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Safety, Pharmacokinetics, and Clinical Effects of Cinacalcet (AMG 073) in Primary Hyperparathyroidism

11 december 2018 uppdaterad av: Amgen

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 6-week Dose-Ranging Study to Assess the Safety, Pharmacokinetics, and Clinical Effects of an Oral Calcimimetic Agent (AMG 073) in Primary Hyperparathyroidism

The primary objective was to assess the safety and tolerability of cinacalcet in adults with primary hyperparathyroidism (HPT) when administered as a single oral once daily doses for 6 consecutive weeks and twice daily for 15 consecutive days.

Studieöversikt

Status

Avslutad

Studietyp

Interventionell

Inskrivning (Faktisk)

48

Fas

  • Fas 2

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Males and females ≥ 18 years of age at screening. In Part 1, females must be postmenopausal (at least 12 months since last menstrual period) or surgically sterile.

    In Part 2, all qualified females replacing a Part 1 subject (i.e., naïve subjects), regardless of reproductive status, may participate if, in the opinion of the principal investigator, an appropriate effective contraceptive method is used throughout the study. All females must have a negative serum pregnancy test within 28 days prior to Baseline (Parts 1 and 2).

  2. Men and women participating in this study must agree to use, in the opinion of the principal investigator, highly effective contraceptive measures throughout the study. All females who are pregnant or breast-feeding are excluded. All subjects must notify the principal investigator if they or their partner suspects a pregnancy.
  3. Diagnosis of primary HPT. A plasma intact PTH concentration ≥ 45 pg/mL on at least two occasions at least 1 week apart during the 12 months prior to baseline (at least one of these determinations should be made during screening), and a corrected total serum calcium concentration (for each 1 g/dL decrease in albumin level below 4.0 g/dL, the calcium value should be increased by 0.8 mg/dL) greater than the upper limit of normal, but no greater than 12.5 mg/dL.
  4. Acceptable renal function, with an estimated creatinine clearance > 50 ml/min as determined by the Cockroft and Gault equation.
  5. Acceptable hepatic function, defined as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin < 2 times the upper limit of normal.
  6. Fasting (8 hours) serum glucose ≤ 130 mg/dL and hemoglobin Alc within the central laboratory's normal range.
  7. Hematology panel, serum clinical chemistry and urinalysis results within normal ranges
  8. Chest x-ray without evidence of active, infectious, inflammatory or malignant process.

Exclusion Criteria:

  1. Any unstable medical condition, defined as having been hospitalized within 28 at prior to baseline, or otherwise unstable in the judgement of the investigator.
  2. Received within 21 day prior to baseline, therapy with systemic glucocorticoids, lithium, tricyclic antidepressants, thioridazine, haloperidol, flecainide, or other drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 CYP 2D6, drugs that affect renal tubular calcium handling (e.g. thiazide or loop diuretics), and drugs that affect bone metabolism (e.g. calcitonin, selective estrogen receptor modulators [SERMs])
  3. Received, within 90 days prior to Baseline, chronic therapy with bisphosphonates or fluoride.
  4. Known alcohol abuse, or use of illicit drugs, within 12 months prior to Baseline
  5. Experienced a myocardial infarction (MI) within 6 months prior to Baseline
  6. A ventricular rhythm disturbance requiring current treatment
  7. Received investigational drugs within 28 days prior to Baseline
  8. A history of seizures within 12 months prior to Baseline
  9. A history (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
  10. A gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
  11. A Body Mass Index (BMI) < 15 or > 40, obtained during screening
  12. An inability to swallow capsules
  13. Sarcoidosis, tuberculosis, or other diseases known to cause hypercalcemia
  14. Fasting spot urine calcium/creatinine ratio (mg) < 0.05
  15. A psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
  16. Any other condition that might reduce the chance of obtaining data (eg, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent.
  17. For Part 2, a subject from Part 1 who discontinued treatment early

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Sekventiell tilldelning
  • Maskning: Dubbel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Placebo-jämförare: Placebo
In Part 1 participants received placebo capsules orally once a day for 6 weeks. In Part 2 participants received placebo capsules twice a day for 15 days.
Kapslar för oral administrering
Experimentell: Cinacalcet 50 mg QD
In Part 1 participants received 50 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 30 mg cinacalcet capsules twice a day for 15 days.
Capsule for oral administration
Andra namn:
  • AMG 073
  • Sensipar®
  • Mimpara®
Experimentell: Cinacalcet 75 mg QD
In Part 1 participants received 75 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 40 mg cinacalcet capsules twice a day for 15 days.
Capsule for oral administration
Andra namn:
  • AMG 073
  • Sensipar®
  • Mimpara®
Experimentell: Cinacelcet 100 mg QD
In Part 1 participants received 100 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 50 mg cinacalcet capsules twice a day for 15 days.
Capsule for oral administration
Andra namn:
  • AMG 073
  • Sensipar®
  • Mimpara®

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Number of Participants with Adverse Events in Part 1 and Part 2
Tidsram: 6 weeks in Part 1 and 15 days in Part 2
6 weeks in Part 1 and 15 days in Part 2

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percent Change from Baseline in Serum Calcium Concentration
Tidsram: Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
Area Under the Serum Calcium Concentration-time Curve from 0 to 24 Hours After Dosing (AUC0-24) in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Area Under the Serum Calcium Concentration-time Curve from 0 to 12 Hours After Dosing (AUC0-12) in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Minimum Serum Calcium Concentration in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Minimum Serum Calcium Concentration in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Cumulative Time When Serum Calcium was Below Baseline During the 24-hour Dosing Interval in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time When Serum Calcium was Below Baseline During the 12-hour Dosing Interval in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Cumulative Time Over the Day When Serum Calcium was ≤ 10.3 mg/dL In Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time Over the Day When Serum Calcium was ≤ 10.3 mg/dL In Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Percent Change from Baseline in Plasma Intact parathyroid Hormone (iPTH) Concentration
Tidsram: Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
Area Under the Plasma iPTH Concentration-time Curve from 0 to 24 Hours After Dosing (AUC0-24) in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Area Under the Plasma iPTH Concentration-time Curve from 0 to 12 Hours After Dosing (AUC0-12) in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Minimum iPTH Concentration in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Minimum iPTH Concentration in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Time of Minimum iPTH Concentration in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Time of Minimum iPTH Concentration in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Cumulative Time When iPTH was Below Baseline During the 24-hour Dosing Interval in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time When iPTH was Below Baseline During the 12-hour Dosing Interval in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Cumulative Time iPTH was Below 45 pg/mL in Part 1
Tidsram: Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time iPTH was Below 45 pg/mL in Part 2
Tidsram: Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Percent Change from Baseline in Serum Calcitonin Concentration
Tidsram: Baseline and days 8, 15, and 43 in Part 1
Baseline and days 8, 15, and 43 in Part 1
Percentage of Participants with Serum Calcitonin Concentration Less than 10 pg/mL
Tidsram: Baseline and days 8, 15 and 43 in Part 1
Baseline and days 8, 15 and 43 in Part 1
Percent Change from Baseline in Bone-specific Alkaline Phosphatase (BALP) Concentration
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percentage of Participants with BALP Concentration Within Normal Range
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of BALP is 2.9 to 20.1 ng/mL for men 20 to 79 years of age and and 3.7 to 20.9 ng/mL for women 20 to 79 years of age.
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percent Change from Baseline in Serum N-telopeptide (NTx) Concentration
Tidsram: Baseline and days 8 and 15 in Part 1
Baseline and days 8 and 15 in Part 1
Percentage of Participants with Serum NTx Concentration Within Normal Range
Tidsram: Baseline and days 8 and 15 in Part 1
Normal range of serum NTx is 5.4 to 24.2 nmoL bone collagen equivalents (BCE)/L for men, 6.2 to 19.0 nmoL BCE/L for premenopausal women, and 5.3 to 35.8 nmol BCE/L for postmenopausal women (≥ 55 years).
Baseline and days 8 and 15 in Part 1
Percent Change from Baseline in Urinary NTx Concentration
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percentage of Participants with Urinary NTx Concentration Within Normal Range
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of urinary NTx is is 0.0 to 85.0 nmoL BCE/mmoL creatinine for men, 5.0 to 65.0 nmoL BCE/mmoL creatinine for premenopausal women, and 0.0 to 130.0 nmoL BCE/mmoL creatinine for postmenopausal women [≥ 55 years).
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percent Change from Baseline in Urinary Calcium/Creatinine Ratio
Tidsram: Baseline and days 8 and 15 in Part 1
Baseline and days 8 and 15 in Part 1
Percent Change from Baseline in Urinary Calcium Concentration
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percentage of Participants with Urinary Calcium Concentration Within Normal Range
Tidsram: Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of urinary calcium is 50 to 300 mg/24 hours.
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percent Change from Baseline in 1,25-Dihydroxy Vitamin D
Tidsram: Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
Percentage of Participants with 1,25-Dihydroxy Vitamin D Concentration in the Normal Range
Tidsram: Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
The normal range for 1,25-dihydroxy vitamin D3 is 16.0 to 65.0 pg/mL.
Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
Percent Change from Baseline in Urinary and Serum Phosphorus Concentrations
Tidsram: Baseline and days 8, 15, and 22 in Part 2
Baseline and days 8, 15, and 22 in Part 2

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

29 september 1998

Primärt slutförande (Faktisk)

13 december 1999

Avslutad studie (Faktisk)

13 december 1999

Studieregistreringsdatum

Först inskickad

11 december 2018

Först inskickad som uppfyllde QC-kriterierna

11 december 2018

Första postat (Faktisk)

13 december 2018

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

13 december 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

11 december 2018

Senast verifierad

1 december 2018

Mer information

Termer relaterade till denna studie

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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