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

Acromegaly Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01673646
• Other study ID #: CSOM230C1202
• Status: Completed
• Phase: Phase 2
• Start date: October 16, 2012
• Est. completion date: April 10, 2017

Study information

• Verified date: July 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: April 10, 2017
• Est. primary completion date: April 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acromegaly
• Gigantism
• Pituitary Diseases
• Pituitary Gigantism

Intervention

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.

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Fukushima city	Fukushima
Japan	Novartis Investigative Site	Isehara	Kanagawa
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kagoshima city	Kagoshima
Japan	Novartis Investigative Site	Kawasaki	Kanagawa
Japan	Novartis Investigative Site	Kitakyushu-city	Fukuoka
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Minato ku	Tokyo
Japan	Novartis Investigative Site	Morioka	Iwate
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Shizuoka-city	Shizuoka
Japan	Novartis Investigative Site	Suita city	Osaka
Japan	Novartis Investigative Site	Tokorozawa city	Saitama
Japan	Novartis Investigative Site	Toyoake city	Aichi
Japan	Novartis Investigative Site	Yamagata
Japan	Novartis Investigative Site	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	Change From Baseline in Prolactin	Change in prolactin levels from baseline	Baseline, Months 3, 6, 9, 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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