Efficacy and Safety of Pasireotide LAR (Long-acting Release) in Japanese Patients With Acromegaly or Pituitary Gigantism

A Multicenter, Open-label, Randomized, Phase II Study to Evaluate Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Pasireotide LAR in Japanese Patients With Active Acromegaly or Pituitary Gigantism

To evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of pasireotide LAR in Japanese patients with active acromegaly or pituitary gigantism. Primary objective was to assess the total-group efficacy of pasireotide LAR on the reduction of mean GH levels to < 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) at 3 months of study treatment.

Study Overview

• Status: Completed
• Conditions: Acromegaly; Pituitary Gigantism
• Intervention / Treatment: Drug: Pasireotide LAR

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260 8677
    • Novartis Investigative Site
  • Osaka, Japan, 534-0021
    • Novartis Investigative Site
  • Yamagata, Japan, 990 9585
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 466 8560
      • Novartis Investigative Site
    • Toyoake city, Aichi, Japan, 470 1192
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 807-8556
      • Novartis Investigative Site
  • Fukushima
    • Fukushima city, Fukushima, Japan, 960 1295
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
  • Iwate
    • Morioka, Iwate, Japan, 020 8505
      • Novartis Investigative Site
  • Kagoshima
    • Kagoshima city, Kagoshima, Japan, 890 8520
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
    • Kawasaki, Kanagawa, Japan, 211-8510
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 222-0036
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 612-8555
      • Novartis Investigative Site
  • Miyagi
    • Sendai city, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 530-8480
      • Novartis Investigative Site
    • Suita city, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Saitama
    • Tokorozawa city, Saitama, Japan, 359 8513
      • Novartis Investigative Site
  • Shizuoka
    • Shizuoka-city, Shizuoka, Japan, 420-8527
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113 8655
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Minato ku, Tokyo, Japan, 105-8470
      • Novartis Investigative Site
    • Shinjuku ku, Tokyo, Japan, 162 8666
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with medication naïve acromegaly or pituitary gigantism
• Patients with inadequately controlled acromegaly or pituitary gigantism

Exclusion Criteria:

• Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1c >8%
• Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment
• Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF > 470 ms, hypokalemia, hypomagnesemia, hypocalcemia, family history of long QT syndrome, or patients receiving a concomitant medication known to prolong QT interval

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pasireotide LAR 20mg; Enrolled patients were randomized to 20mg pasireotide LAR.	Drug: Pasireotide LAR; Intramuscular administration of pasireotide LAR was repeated every month (1 month = 28 days) for 12 months in core phase. It was permitted to increase the dose up to 60 mg in a patient showing the following biochemical test results after 3 and 6 months of study treatment: mean GH levels ≥2.5 µg/L and/or IGF-1 > ULN. In the event of any problem with tolerability, it was permitted to reduce the next lower dosage level at any time.; Other Names: SOM230
EXPERIMENTAL: Pasireotide LAR 40mg; Enrolled patients were randomized to 40mg pasireotide LAR.	Drug: Pasireotide LAR; Intramuscular administration of pasireotide LAR was repeated every month (1 month = 28 days) for 12 months in core phase. It was permitted to increase the dose up to 60 mg in a patient showing the following biochemical test results after 3 and 6 months of study treatment: mean GH levels ≥2.5 µg/L and/or IGF-1 > ULN. In the event of any problem with tolerability, it was permitted to reduce the next lower dosage level at any time.; Other Names: SOM230
EXPERIMENTAL: Pasireotide LAR 60mg; Enrolled patients were randomized to 60mg pasireotide LAR.	Drug: Pasireotide LAR; Intramuscular administration of pasireotide LAR was repeated every month (1 month = 28 days) for 12 months in core phase. It was permitted to increase the dose up to 60 mg in a patient showing the following biochemical test results after 3 and 6 months of study treatment: mean GH levels ≥2.5 µg/L and/or IGF-1 > ULN. In the event of any problem with tolerability, it was permitted to reduce the next lower dosage level at any time.; Other Names: SOM230

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total-group Response Rate at Month 3	Percentage of participants with a reduction of mean growth hormone (GH) levels to < 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses	Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate at Month 3 by Randomized Dose Level	Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3 months in each starting dose.	Month 3
GH Response at Month 3 by Randomized Dose	Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L at 3 months.	Month 3
IGF-1 Response at Month 3 by Randomized Dose	Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 3 months.	Month 3
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase)	Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3, 6, 9 and 12 months	Months 3, 6, 9 & 12
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase)	This refers to the percentage of participants with a reduction of growth hormone (GH) response rates to <2.5 ug/L over time.	Months 3, 6, 9, 12
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase)	This refers to the percentage of participants with the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits by visit.	Months 3, 6, 9, 12
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level	Ctrough: The trough level concentration on day 28, 3 months post 1st, 2nd and 3rd injections of Pasireotide LAR. Cmax: The maximum concentration 3 months post the 1st injection and 3rd injection of LAR.	Ctrough: Day 28 after each injection 1-3, Cmax: 3 months after injections 1 and 3
Summary of Pasireotide LAR PK Parameter of Accumulation Ratio Randomized Dose Level	The accumulation ratio was calculated as a ratio of (Ctrough day28, 3rd injection/Ctrough day28, 1st injection).	Day 28 after injections 1 and 3
Change of Tumor Volume From Baseline	This shows the change in tumor volume from baseline to month 6 and from baseline to month 12 in patients treated with pasireotide LAR.	Baseline, Months 6 , 12
Change in Mean GH Levels From Baseline	This shows the change in mean GH levels from baseline in median GH levels by visit.	Baseline, Months 2.75, 3, 6, 9, 12, 18, 24
Change in Ring Size From Baseline	Change of clinical signs from baseline: ring size. In Japan, ring sizes are specified using a numerical scale, that only has whole sizes, and does not have simple linear correlation with diameter or circumference. Only numbers are used ranging from 1 to 27. For instance, a ring size of 1 in Japan is equivalent to an inside circumference ring size of 38.86 mm and a ring size of 27 in Japan is equivalent to an inside circumference ring size of 70.15 mm.	Baseline, Months 3, 6, 9, 12
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase)	Number of participants with a change of clinical signs from baseline (BL): headache (HA), fatigue (FA), perspiration (PE), paresthesias (PA), osteoarthralgia (OS)	12 Months (Core phase)
Change From Baseline in Prolactin	Change in prolactin levels from baseline	Baseline, Months 3, 6, 9, 12
Total-group Response Rate by Visit (Extension Phase)	Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) a18 and 24 months of study treatment.	Months 18, 24
Percentage of Overall Participants With the Reduction of Mean GH Levels to <2.5 ug/L by Visit (Extension Phase)	Percentage of participants with a reduction of mean GH levels to < 2.5µg/L at 18 and 24 months of study treatment	Months 18, 24
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Extension Phase)	Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 18 and 24 months of study. treatment	Months 18, 24
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase)	This shows a change of mean GH levels and somatostatin analogues (SSAs) from baseline in extension phase	Baselnine, Months 2.75, 3, 6, 9, 12, 18, 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 16, 2012
• Primary Completion (ACTUAL): April 10, 2017
• Study Completion (ACTUAL): April 10, 2017

Study Registration Dates

• First Submitted: August 16, 2012
• First Submitted That Met QC Criteria: August 23, 2012
• First Posted (ESTIMATE): August 28, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Pituitary adenoma; acromegaly; Phase II; SOM230; growth disorder; gigantism; pituitary gigantism; Pasireotide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Bone Diseases, Developmental; Pituitary Diseases; Acromegaly; Gigantism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230C1202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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