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Efficacy and Safety of Pasireotide LAR in Japanese Patients With Acromegaly or Pituitary Gigantism

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01673646
First received: August 16, 2012
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

To evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of pasireotide LAR in Japanese patients with active acromegaly or pituitary gigantism. Primary objective is 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 IGF-1 at 3 months of study treatment.


Condition Intervention Phase
Acromegaly, Pituitary Gigantism
Drug: SOM230LAR
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Growth Hormone (GH) and glucagon-like peptide-1 (IGF-1) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Assess the total-group efficacy of pasireotide LAR on the reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 at 3 months of study treatment.


Secondary Outcome Measures:
  • GH and IGF-1 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Assess the effect of each starting dose pasireotide LAR on the reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 at 3 months of study treatment

  • Profile of Pharmacokinetics [ Time Frame: predose, day2, day15, day22 and every 28days up to 12 months ] [ Designated as safety issue: No ]
    Assess Ctrough, Cmax and accumulation ratio of pasireotide LAR 20 mg, 40 mg and 60 mg

  • Number of patients with Adverse Events as a Measure of safety and tolerability [ Time Frame: every 28days up to 24 months ] [ Designated as safety issue: Yes ]
    Assess the tolerability and safety profile of pasireotide LAR at 3 months and during and after the 24- month study treatment using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale

  • GH [ Time Frame: Baeline, 3 months, 6 months, 9 months, 12 months, 18 months and 24 motnhs ] [ Designated as safety issue: No ]
    Assess the effect of pasireotide LAR on the reduction of mean GH levels to < 2.5 µg/L at 3, 6, 9, 12, 18 and 24 months of study treatment and the change of mean GH level from baseline

  • IGF-1 [ Time Frame: 3 months, 6 months, 9 months, 12 months, 18 months and 24 months ] [ Designated as safety issue: No ]
    Assess the effect of pasireotide LAR on the normalization of IGF-1 at 3, 6, 9, 12, 18, 24 months of study treatment

  • Tumor volume [ Time Frame: Baseline, 6 months and 12 months ] [ Designated as safety issue: No ]
    Assess the effect of pasireotide LAR on the change of tumor volume at 6and 12 months of study treatment

  • Change of clinical signs from baseline [ Time Frame: Baseline, every 3months up to 12 months ] [ Designated as safety issue: No ]
    Clinical signs include ring size, headache, fatigue, perspiration, paresthesias, osteoarthralgia

  • Prolactin (PRL) [ Time Frame: Baseline, every 3 months up to 12 months ] [ Designated as safety issue: No ]
    Assess the effect of pasireotide LAR on the change of PRL level from baseline

  • Profile of Pharmacokinetic/Pharmacodynamic [ Time Frame: Day1, Day2, Day15, Day22, every 28days up to 6 months ] [ Designated as safety issue: No ]
    Assess the relationship between pasireotide plasma concentration and GH/IGF-1

  • GH and IGF-1 [ Time Frame: 6months, 9 months, 12 months 18 months and 12 months ] [ Designated as safety issue: No ]
    Assess the total-group efficacy of pasireotide LAR on the reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 at 6, 9, 12, 18, 24 months of study treatment.


Enrollment: 33
Study Start Date: October 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOM230LAR 20mg
10 enrolled patients will be randomized to 20mg pasireotide LAR.
Drug: SOM230LAR
Intramuscular administration of pasireotide LAR will be repeated every month (1 month = 28 days) for 12 months in core phase. It is 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 is permitted to reduce the next lower dosage level at any time.
Experimental: SOM230LAR 40mg
10 enrolled patients will be randomized to 40mg pasireotide LAR.
Drug: SOM230LAR
Intramuscular administration of pasireotide LAR will be repeated every month (1 month = 28 days) for 12 months in core phase. It is 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 is permitted to reduce the next lower dosage level at any time.
Experimental: SOM230LAR 60mg
10 enrolled patients will be randomized to 60mg pasireotide LAR.
Drug: SOM230LAR
Intramuscular administration of pasireotide LAR will be repeated every month (1 month = 28 days) for 12 months in core phase. It is 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 is permitted to reduce the next lower dosage level at any time.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673646

Locations
Japan
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 466-8560
Novartis Investigative Site
Toyoake, Aichi, Japan, 470-1192
Novartis Investigative Site
Chiba-city, Chiba, Japan, 260-8677
Novartis Investigative Site
Fukuoka-city, Fukuoka, Japan, 812-8582
Novartis Investigative Site
Kitakyushu, Fukuoka, Japan, 807-8556
Novartis Investigative Site
Fukushima-city, Fukushima, Japan, 960-1295
Novartis Investigative Site
Sapporo-city, Hokkaido, Japan, 060-8648
Novartis Investigative Site
Kobe-city, Hyogo, Japan, 650-0017
Novartis Investigative Site
Morioka-city, Iwate, Japan, 020-8505
Novartis Investigative Site
Kagoshima-city, Kagoshima, Japan, 890-8520
Novartis Investigative Site
Isehara-city, Kanagawa, Japan, 259-1193
Novartis Investigative Site
Kawasaki, Kanagawa, Japan, 211-8510
Novartis Investigative Site
Yokohama, Kanagawa, Japan, 222-0036
Novartis Investigative Site
Kyoto-city, Kyoto, Japan, 612-8555
Novartis Investigative Site
Sendai-city, Miyagi, Japan, 980-8574
Novartis Investigative Site
Okayama-city, Okayama, Japan, 700-8558
Novartis Investigative Site
Osaka-city, Osaka, Japan, 534-0021
Novartis Investigative Site
Suita-city, Osaka, Japan, 565-0871
Novartis Investigative Site
Tokorozawa-city, Saitama, Japan, 359-8513
Novartis Investigative Site
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
Osaka, Japan, 530-8480
Novartis Investigative Site
Shizuoka, Japan, 420-8527
Novartis Investigative Site
Yamagata, Japan, 990-9585
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01673646     History of Changes
Other Study ID Numbers: CSOM230C1202
Study First Received: August 16, 2012
Last Updated: July 7, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Novartis:
SOM230, Pasireotide, acromegaly, Phase II

Additional relevant MeSH terms:
Acromegaly
Gigantism
Bone Diseases
Bone Diseases, Developmental
Bone Diseases, Endocrine
Brain Diseases
Central Nervous System Diseases
Endocrine System Diseases
Hyperpituitarism
Hypothalamic Diseases
Musculoskeletal Diseases
Nervous System Diseases
Pituitary Diseases

ClinicalTrials.gov processed this record on November 25, 2014