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

Novartis Pharmaceuticals33 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acromegaly Pituitary Gigantism

Interventions

Pasireotide LARDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (27)

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Outcomes

Primary Outcomes

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

Time frame: Month 3

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Months 3, 6, 9, 12

Data from ClinicalTrials.gov

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Novartis Investigative Site

Toyoake, Aichi-ken, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Kitakyushu, Fukuoka, Japan

Novartis Investigative Site

Fukushima, Fukushima, Japan

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Novartis Investigative Site

Kobe, Hyōgo, Japan

Novartis Investigative Site

Morioka, Iwate, Japan

Novartis Investigative Site

Kagoshima, Kagoshima-ken, Japan

Novartis Investigative Site

Isehara, Kanagawa, Japan

...and 17 more locations

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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 12 Months (Core phase)

Change From Baseline in Prolactin

Change in prolactin levels from baseline

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baselnine, Months 2.75, 3, 6, 9, 12, 18, 24