A Study to Learn if Recombinant Human Parathyroid Hormone [rhPTH(1-84)] Can Improve Symptoms and Metabolic Control in Adults With Hypoparathyroidism (BALANCE)

A Randomized, Double-blind, Placebo-controlled, Adaptive Study to Evaluate Symptom Improvement and Metabolic Control Among Adult Subjects With Symptomatic Hypoparathyroidism Treated With Recombinant Human Parathyroid Hormone [rhPTH(1-84)]

Recombinant human parathyroid hormone, also known as if rhPTH(1-84), is a medicine to treat people with Hypothyroidism. The main aim of this study is to learn if rhPTH(1-84) can improve symptoms in adults with hypoparathyroidism.

In this study, participants will receive 1 of 2 treatments: rhPTH(1-84) or a placebo. A placebo looks like the medicine being studied but does not have medicine in it. In this study, the placebo will be a standard treatment which is either active Vitamin D, or active Vitamin D with calcium. Active Vitamin D is a form of vitamin D that has a faster effect on the body. These treatments will be given as a daily injection just under the skin. Participants will not know which treatment they received, nor will their study doctors. This is to help make sure the results are more reliable. All participants will also take active vitamin D and calcium supplements during treatment.

Participants will record their symptoms in a tool called the hypoparathyroidism symptom diary. This tool is used to assess symptoms and their impact and will give an overall score for each participant.

The study doctors will also check for side effects from the study treatments.

After treatment, researchers will check if there is any difference in the diary scores between the 2 treatment groups. A difference in score means there is a difference in symptoms and their impact. From this, researchers will learn if symptoms have improved for participants treated with rhPTH(1-84) compared with those treated with placebo.

Study Overview

• Status: Completed
• Conditions: Hypoparathyroidism
• Intervention / Treatment: Biological: Placebo; Biological: rhPTH (1-84)

Detailed Description

24 SEPTEMBER 2020: The temporary enrollment stop of new patients into this study due to the COVID-19 pandemic has been lifted in one or more countries, and the study is now again enrolling new patients. However, some countries/sites may still have paused the enrollment of new patients due to the pandemic.

20 APRIL 2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Quebec-Universite Laval
  • Saint John's, Canada, A1B3V6
    • Eastern Health - Health Sciences Center- General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority (Capital District Health Authority)
  • Ontario
    • Oakville, Ontario, Canada, L6M 1M1
      • Bone Research and Education Centre
• Denmark
  • Odense C, Denmark, 5000
    • Odense Universitetshospital
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Aarhus Universitetshospital
• France
  • Angers, France, 49933
    • CHU Angers
  • Besançon, France, 25030
    • Hôpital Jean Minjoz
  • Le Kremlin-Bicêtre, France, 94275
    • CHU Bicêtre
  • Lille, France, 59000
    • CHRU Lille
• Germany
  • Sachsen
    • Dresden, Sachsen, Germany, 1307
      • Universitätsklinikum Carl Gustav Carus an der TU Dresden
• Italy
  • Firenze, Italy, 50139
    • Universita di Firenze, Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
  • Roma, Italy, 128
    • Universita Campus Bio Medico di Roma
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • Leids Universitair Medisch Centrum
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • VU Medisch Centrum
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus
  • Oslo, Norway, 372
    • Oslo Universitetssykehus HF Rikshospitalet
  • Oslo, Norway, N-0514
    • Oslo universitetssykehus Aker
• Portugal
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitario de Coimbra EPE
  • Matosinhos, Portugal, 4464-513
    • Unidade Local de Saúde de Matosinhos SA
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, E.P.E.
• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jiménez Díaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Córdoba
    • Cordoba, Córdoba, Spain
      • C.H. Regional Reina Sofia - PPDS
  • Madrid
    • Pozuelo De Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary - PPDS
  • Dundee City
    • Dundee, Dundee City, United Kingdom, DD1 9SY
      • Ninewells Hospital - PPDS
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Michigan Bone and Mineral Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - PPDS
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East PA
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has an understanding, ability, and willingness to fully comply with study procedures and restrictions.
• Is able to voluntarily provide a signed and dated informed consent form before any study-related procedures are performed.
• Is an adult male or female 18 to 85 years of age, inclusive.
• In participants 18-25 years of age, has radiological evidence of epiphyseal closure based on bone age X-ray (single posteroanterior X-ray of left wrist and hand) before randomization.
• Has chronic hypoparathyroidism with onset 12 months or more before screening. The diagnosis of hypoparathyroidism is established based on hypocalcemia in the setting of inappropriately low serum PTH levels.
• During the Week -3 screening visit, the participant reports by history at least 2 of the following symptoms related to hypoparathyroidism occurring within the 2 weeks before Week -3 visit: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog).
• The participant must have a Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale Sum Score of greater than or equal to (>=) 10 during the 14-day period immediately prior to the baseline (Week 0) visit (Day -14 to Day -1). In addition, the participant must have at least 4 HPT-SD diaries completed in the first 7 day period and at least 4 HPT-SD diaries completed in second 7 day period.

• Must be treated with active vitamin D (calcitriol or alfacalcidol) alone or in conjunction with calcium supplements for at least 4 months prior to the screening visit.

  1. The participant must be taking >= 0.5 microgram (mcg)/day of calcitriol or >=1.0 mcg/day of alfacalcidol.
  2. If the participant is treated with a lower dose of active vitamin D the participant must also be taking calcium supplements of at least 800 milligrams per day (mg/day) of elemental calcium.
• Has serum thyroid-stimulating hormone (TSH) results within normal laboratory limits at screening for all participants not receiving thyroid hormone replacement therapy. For participants on thyroid hormone replacement therapy, the thyroid hormone dose must have been stable for at least 4 weeks before screening, and serum TSH level must be within the central laboratory normal range. A serum TSH level below the lower limit of the normal range but not undetectable in participant treated with thyroid hormone may be allowed if there is no anticipated need for a change in thyroid hormone dose during the trial.
• Has serum 25-hydroxyvitamin D levels >=50 nmol/L (nanomoles per liter) (20 nanograms per milliliter [ng/mL]) and less than (<) 1.5 times the upper limit of normal (ULN) for the central laboratory normal range.
• Has estimated glomerular filtration rate (eGFR) greater than (>) 30 milliliter per minute per 1.73 square meters (ml/min/1.73m^2).
• Prior to randomization, is able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh.
• Willing to use oral active vitamin D and calcium supplements provided for the study unless directed to remain on the supplements used prior to enrollment in the current study by the investigator after consultation with the medical monitor.
• With regard to female participants: women who are postmenopausal (12 consecutive months of spontaneous amenorrhea and age >= 51 years) and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at randomization and be willing to comply with any applicable contraceptive requirements of the protocol and pregnancy testing for the duration of the study.

Exclusion Criteria:

• History of hypoparathyroidism resulting from a known activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as poorly controlled hyperthyroidism; Paget disease; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver (Child-Pugh score >9) (US FDA, 2003), or renal disease; Cushing syndrome; rheumatoid arthritis; myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer); primary or secondary hyperparathyroidism; or documented parathyroid carcinoma within the previous 5 years, acromegaly, or multiple endocrine neoplasia types 1 and 2.
• Very low or very high blood calcium level (eg, ACSC <1.87 mmol/L [<7.5 mg/dL] or >=2.97 mmol/L [>=11.9 mg/dL]) at the Week -3 screening visit. Results from the central laboratory must be used for this assessment.
• Blood calcium level above the ULN at the baseline (Week 0) visit. Results from a local laboratory may be used for this assessment.
• Use of prohibited medications, such as loop and thiazide diuretics, phosphate binders (other than calcium carbonate), digoxin, lithium, methotrexate, or systemic corticosteroids, within respective prohibited periods.
• Participation in any other investigational study in which receipt of investigational drug or device occurred within 6 months before screening for this study. Prior treatment with PTH-like drugs (whether commercially available or through participation in an investigational study), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 3 months before screening.
• Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride, within the prohibited period.
• Use of oral bisphosphonates within the previous 6 months or intravenous bisphosphonate preparations within the previous 24 months before screening.
• Nonhypocalcemic seizure disorder with a history of a seizure within the previous 6 months before screening. Participants with a history of seizures that occur in the setting of hypocalcemia are allowed.
• The participant is at increased baseline risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of external beam or implant radiation therapy involving the skeleton.
• Any disease or condition that, in the opinion of the investigator, may require treatment or make the participant unlikely to fully complete the study or any condition that presents undue risk from the investigational product or procedures. For example, illness that is anticipated to be chronic and not transient.
• Pregnant or lactating women.
• Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
• History of diagnosed drug or alcohol dependence within the previous 3 years.
• Poorly controlled short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn disease.
• Chronic or severe cardiac disease including but not limited to heart failure (according to the New York Heart Association classification Class II to Class IV) (Dolgin and NYHA, 1994), arrhythmias, bradycardia (resting heart rate <50 beats/minute).
• History of cerebrovascular accident.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to rhPTH (1-84) as subcutaneous (SC) injection once daily (QD) with active vitamin D and calcium supplements up to 31.3 weeks.	Biological: Placebo; Placebo QD SC injection.
Experimental: rhPTH (1-84); Participants received rhPTH (1-84) 50 microgram (mcg) SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.	Biological: rhPTH (1-84); rhPTH (1-84) SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Subscale Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Negative change in scores indicates improvement. A mixed model for repeated measures (MMRM) was used for analysis.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26	The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT-Fatigue questionnaire are each measured on a 5-point Likert scale, where 0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit and 4=Very much. Thus, the total score ranges from 0 to 52. High scores represent less fatigue. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26	The SF-36 is a validated instrument that questions participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in PCS derived from SF-36v2 at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Subscale Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The impact subscale score was computed as the average of impact items 10-13 scores with no impact item score was non-missing. Negative change in scores indicates improvement. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The change in individual symptom item scores was reported. Negative change in scores indicates improvement. MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Anxiety (Item 8) Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. The anxiety item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the anxiety item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. The sadness or depression item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. Negative change in scores indicates improvement. MMRM was used for analysis.	Baseline, Week 26
Number of Participants With Response at Week 26 [Early Termination (ET)]	Response was defined as a 30% reduction in HypoPT-SD symptom subscale score from baseline. The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; and for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Data reported also includes results for early terminated participants.	Baseline up to Week 26
Change From Baseline in the Most Bothersome Symptom Score at Week 26	The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The Most Bothersome Symptom Score was analyzed. Negative change in scores indicates improvement. MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Perceived Cognitive Impairments (PCI) Score at Week 26	The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. The perceived cognitive impairment and the impact on quality of life domains were assessed in this study. These 2 domains include 22 items rated on a 5-point scale. The perceived cognitive impairments subscale contains 18 items and each item has a 5-point ordinal response scale (0=Never, 1= About once a week, 2 = Two to three times a week, 3= Nearly every day, 4 = Several times a day). Each item score is calculated as (4 minus item response), and the subscale score is [sum of (4 minus item response)]*18/(number of items answered)]. The perceived cognitive impairment subscale score ranges from 0 to 72, with higher scores indicate better cognitive function. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Impact on Quality of Life (QoL) Score at Week 26	The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. The perceived cognitive impairment and the impact on quality of life domains were assessed in this study. These 2 domains include 22 items rated on a 5-point scale. The impact on quality of life domain contains 4 items and each item has a 5-point ordinal response scale (0=Never, 1= About once a week, 2 = Two to three times a week, 3= Nearly every day, 4 = Several times a day). Each item score is calculated as (4 minus item response), and the subscale score is [sum of (4 minus item response)]*4/(number of items answered)]. The impact on quality of life subscale score ranges from 0 to 16 with higher score indicates better cognitive function. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26	The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the score of individual domains of SF-36v2 at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26	The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the MCS of SF-36v2 at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26	WPAI assessed impact of HypoPT on work productivity and daily activities. Concepts that WPAI: Hypoparathyroidism measures include time missed from work and impairment of work and other regular activities due to specific health problem (HypoPT). WPI was calculated based on 4 items including Q2: hours of work missed due to HPT; Q4: actual hours worked; Q5: HPT effect on productivity at work; Q6: HPT effect on daily activities. Scores for 4 subscales were calculated as Percent work time missed due to problem: Q2/(Q2+Q4)*100; Percent impairment while working due to problem: Q5/10*100; Percent overall work impairment due to problem: Q2/(Q2+Q4)+[(1(Q2/(Q2+Q4)))x(Q5/10)]*100; Percent activity impairment due to problem: Q6/10*100. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. Change from baseline in questionnaire response was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26	The PGI-S is a global index that can be used to rate the severity of a specific condition. The PGI-S is a rating scale that asks the respondent to best describe how their symptoms severity. Response options are assessed as per 5-point scale: no symptoms (0), mild (1), moderate (2), severe (3), and very severe (4). Mean change in scores of PGI-S at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26	The PGI-C is verbal rating scale asks the respondent to best describe change in symptoms compared to the beginning of study. Response options are assessed using a 7-point scale: very much improved (0), much improved (1), minimally improved (2), no change (3), minimally worse (4), much worse (5), and very much worse (6). Negative change indicates improvement. Mean change in scores of PGI-C at Week 26 was be reported.	Baseline, Week 26
Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24	Neurocognitive test battery included tests evaluating frontal-executive domain, which encompasses functions attributable to prefrontal cortex and its connections to basal ganglia (mostly striatum). Tests included the CogState (CS) Brief Battery (including the Detection: speed [range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)], Identification: speed [range from 2.001 to 6; LS indicate IMP], One Card Learning: accuracy [range from 0 to 1.5708; higher scores (HS) indicate IMP], One Back: speed [range from 2.001 to 6; LS indicate IMP]), CS Groton Maze Learning Test: total errors (range from 0 to infinity; LS indicate IMP), CS International Shopping List Task (ISLT): number of correct responses (range from 0 to infinity; HS indicate IMP), and CS ISLT -Delayed Recall: number of correct responses (range from 0 to infinity; HS indicate IMP). Change in in-clinic neurocognitive assessment scores at Week 24 was reported. Analysis of Covariance (ANCOVA) was used for analysis.	Baseline, Week 24
Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26	Neurocognitive test battery included tests evaluating frontal-executive domain, which encompasses functions attributable to prefrontal cortex and its connections to basal ganglia (mostly striatum). Tests included the CogState (CS) Brief Battery (including the Detection: speed [range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)], Identification: speed [range from 2.001 to 6; LS indicate IMP], One Card Learning: accuracy [range from 0 to 1.5708; higher scores (HS) indicate IMP], One Back: speed [range from 2.001 to 6; LS indicate IMP]). Changes in at-home neurocognitive assessment scores (CS Brief Battery) at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in 24-hour Urine Calcium Excretion at Week 26	Change in 24-hour urine calcium excretion at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Serum Phosphate Level at Week 26	Change in serum phosphate level at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Doses of Active Vitamin D at Week 26	Changes in doses of active vitamin D at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Doses of Calcium Supplements at Week 26	Changes in doses of calcium supplements at Week 26 was reported. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Albumin-corrected Serum Calcium Control at Week 26	Change From Baseline in albumin-corrected serum calcium between 1.875 millimoles per liter (mmol/L) (7.5 milligram per deciliter [mg/dL]) and upper limit of normal (ULN) for the central laboratory normal range at Week 26 was reported.	Week 26
Number of Participants Who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Active Vitamin D Dose and Oral Elemental Calcium Supplement Dose at Week 26	Number of participants achieving composite criteria of the following: albumin-corrected serum calcium between 1.875 mmol/L (7.5 mg/dL) and the ULN for the central laboratory normal range, dose of active vitamin D decreased by 50% and at least a 50% reduction from the baseline oral elemental calcium supplement dose at Week 26 was reported.	Week 26
Change From Baseline in Bone Turnover Marker Bone Specific Alkaline Phosphatase at Week 26	Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Bone Turnover Marker Type I Collagen C-Telopeptides at Week 26	Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.	Baseline, Week 26
Change From Baseline in Bone Turnover Marker Osteocalcin and Procollagen 1 N-Terminal Propeptide at Week 26	Bone turnover markers included serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin. A MMRM was used for analysis.	Baseline, Week 26
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs that started or worsened on or after the date and time of the first dose of investigational product.	From start of study drug administration to 4 weeks post follow-up (up to Week 36)

Collaborators and Investigators

• Sponsor: Shire
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hypocalcemia; Hypoparathyroidism; Parathyroid hormone; rhPTH[1-84)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism
• Other Study ID Numbers: SHP634-401; 2017-000284-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No