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

Primary Purpose

Acromegaly, Pituitary Gigantism

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Pasireotide LAR
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acromegaly focused on measuring SOM230, Pasireotide, acromegaly, Phase II, growth disorder, gigantism, Pituitary adenoma, pituitary gigantism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Pasireotide LAR 20mg

Pasireotide LAR 40mg

Pasireotide LAR 60mg

Arm Description

Enrolled patients were randomized to 20mg pasireotide LAR.

Enrolled patients were randomized to 40mg pasireotide LAR.

Enrolled patients were randomized to 60mg pasireotide LAR.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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
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.
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.
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.
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).
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.
Change in Mean GH Levels From Baseline
This shows the change in mean GH levels from baseline in median GH levels by visit.
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.
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)
Change From Baseline in Prolactin
Change in prolactin levels from baseline
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.
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
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
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

Full Information

First Posted
August 16, 2012
Last Updated
August 12, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01673646
Brief Title
Efficacy and Safety of Pasireotide LAR (Long-acting Release) in Japanese Patients With Acromegaly or Pituitary Gigantism
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
October 16, 2012 (Actual)
Primary Completion Date
April 10, 2017 (Actual)
Study Completion Date
April 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acromegaly, Pituitary Gigantism
Keywords
SOM230, Pasireotide, acromegaly, Phase II, growth disorder, gigantism, Pituitary adenoma, pituitary gigantism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pasireotide LAR 20mg
Arm Type
Experimental
Arm Description
Enrolled patients were randomized to 20mg pasireotide LAR.
Arm Title
Pasireotide LAR 40mg
Arm Type
Experimental
Arm Description
Enrolled patients were randomized to 40mg pasireotide LAR.
Arm Title
Pasireotide LAR 60mg
Arm Type
Experimental
Arm Description
Enrolled patients were randomized to 60mg pasireotide LAR.
Intervention Type
Drug
Intervention Name(s)
Pasireotide LAR
Other Intervention Name(s)
SOM230
Intervention Description
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.
Primary Outcome Measure Information:
Title
Total-group Response Rate at Month 3
Description
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
Time Frame
Month 3
Secondary Outcome Measure Information:
Title
Response Rate at Month 3 by Randomized Dose Level
Description
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.
Time Frame
Month 3
Title
GH Response at Month 3 by Randomized Dose
Description
Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L at 3 months.
Time Frame
Month 3
Title
IGF-1 Response at Month 3 by Randomized Dose
Description
Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 3 months.
Time Frame
Month 3
Title
Total-group Response Rate (GH & IGF-1) Over Time (Core Phase)
Description
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
Time Frame
Months 3, 6, 9 & 12
Title
Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase)
Description
This refers to the percentage of participants with a reduction of growth hormone (GH) response rates to <2.5 ug/L over time.
Time Frame
Months 3, 6, 9, 12
Title
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase)
Description
This refers to the percentage of participants with the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits by visit.
Time Frame
Months 3, 6, 9, 12
Title
Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level
Description
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.
Time Frame
Ctrough: Day 28 after each injection 1-3, Cmax: 3 months after injections 1 and 3
Title
Summary of Pasireotide LAR PK Parameter of Accumulation Ratio Randomized Dose Level
Description
The accumulation ratio was calculated as a ratio of (Ctrough day28, 3rd injection/Ctrough day28, 1st injection).
Time Frame
Day 28 after injections 1 and 3
Title
Change of Tumor Volume From Baseline
Description
This shows the change in tumor volume from baseline to month 6 and from baseline to month 12 in patients treated with pasireotide LAR.
Time Frame
Baseline, Months 6 , 12
Title
Change in Mean GH Levels From Baseline
Description
This shows the change in mean GH levels from baseline in median GH levels by visit.
Time Frame
Baseline, Months 2.75, 3, 6, 9, 12, 18, 24
Title
Change in Ring Size From Baseline
Description
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.
Time Frame
Baseline, Months 3, 6, 9, 12
Title
Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase)
Description
Number of participants with a change of clinical signs from baseline (BL): headache (HA), fatigue (FA), perspiration (PE), paresthesias (PA), osteoarthralgia (OS)
Time Frame
12 Months (Core phase)
Title
Change From Baseline in Prolactin
Description
Change in prolactin levels from baseline
Time Frame
Baseline, Months 3, 6, 9, 12
Title
Total-group Response Rate by Visit (Extension Phase)
Description
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.
Time Frame
Months 18, 24
Title
Percentage of Overall Participants With the Reduction of Mean GH Levels to <2.5 ug/L by Visit (Extension Phase)
Description
Percentage of participants with a reduction of mean GH levels to < 2.5µg/L at 18 and 24 months of study treatment
Time Frame
Months 18, 24
Title
Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Extension Phase)
Description
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
Time Frame
Months 18, 24
Title
Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase)
Description
This shows a change of mean GH levels and somatostatin analogues (SSAs) from baseline in extension phase
Time Frame
Baselnine, Months 2.75, 3, 6, 9, 12, 18, 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466 8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Toyoake city
State/Province
Aichi
ZIP/Postal Code
470 1192
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Kitakyushu-city
State/Province
Fukuoka
ZIP/Postal Code
807-8556
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukushima city
State/Province
Fukushima
ZIP/Postal Code
960 1295
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
060 8648
Country
Japan
Facility Name
Novartis Investigative Site
City
Kobe-shi
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Novartis Investigative Site
City
Morioka
State/Province
Iwate
ZIP/Postal Code
020 8505
Country
Japan
Facility Name
Novartis Investigative Site
City
Kagoshima city
State/Province
Kagoshima
ZIP/Postal Code
890 8520
Country
Japan
Facility Name
Novartis Investigative Site
City
Isehara
State/Province
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Novartis Investigative Site
City
Kawasaki
State/Province
Kanagawa
ZIP/Postal Code
211-8510
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
222-0036
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto-city
State/Province
Kyoto
ZIP/Postal Code
612-8555
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 8574
Country
Japan
Facility Name
Novartis Investigative Site
City
Okayama-city
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
530-8480
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita city
State/Province
Osaka
ZIP/Postal Code
565 0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Tokorozawa city
State/Province
Saitama
ZIP/Postal Code
359 8513
Country
Japan
Facility Name
Novartis Investigative Site
City
Shizuoka-city
State/Province
Shizuoka
ZIP/Postal Code
420-8527
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113 8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8603
Country
Japan
Facility Name
Novartis Investigative Site
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Novartis Investigative Site
City
Minato ku
State/Province
Tokyo
ZIP/Postal Code
105-8470
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku ku
State/Province
Tokyo
ZIP/Postal Code
162 8666
Country
Japan
Facility Name
Novartis Investigative Site
City
Chiba
ZIP/Postal Code
260 8677
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
534-0021
Country
Japan
Facility Name
Novartis Investigative Site
City
Yamagata
ZIP/Postal Code
990 9585
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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

Learn more about this trial

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

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