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

Phase 2

Completed

Conditions: Acromegaly
Pituitary Gigantism

Interventions: Drug: Pasireotide LAR

Registration Number: NCT01673646

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pasireotide LAR 60mg	Pasireotide LAR	Enrolled patients were randomized to 60mg pasireotide LAR.
Pasireotide LAR 20mg	Pasireotide LAR	Enrolled patients were randomized to 20mg pasireotide LAR.
Pasireotide LAR 40mg	Pasireotide LAR	Enrolled patients were randomized to 40mg pasireotide LAR.

Primary Outcome Measures

Name	Time	Method
Total-group Response Rate at Month 3	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

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