Efficacy and Safety of Octreotide (MYCAPSSA™ [Formerly Octreolin™]) for Acromegaly

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chiasma, Inc.
ClinicalTrials.gov Identifier:
NCT01412424
First received: August 5, 2011
Last updated: October 28, 2015
Last verified: October 2015
  Purpose
MYCAPSSA™ (formerly Octreolin™) is a proprietary oral form of the approved injectable medical product octreotide used to treat acromegaly. This study will evaluate the efficacy and safety of MYCAPSSA™ treatment in patients with acromegaly.

Condition Intervention Phase
Acromegaly
Drug: Octreotide capsules
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Oral Octreolin™ in Patients With Acromegaly Who Are Currently Receiving Parenteral Somatostatin Analogs

Resource links provided by NLM:


Further study details as provided by Chiasma, Inc.:

Primary Outcome Measures:
  • Percentage of Responders at the End of the Core Treatment Period [ Time Frame: End of the core treatment period (up to 7 months) ] [ Designated as safety issue: No ]
    A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

  • Percentage of Responders at the End of the Extension Treatment Period [ Time Frame: End of the extension treatment period (up to 13 months) ] [ Designated as safety issue: No ]
    A responder was defined as a participant with a serum insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal (adjusted for age and gender) and a growth hormone (GH) concentration < 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.


Secondary Outcome Measures:
  • Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period [ Time Frame: Baseline and the end of the core treatment period (up to 7 months) ] [ Designated as safety issue: No ]
    Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at Baseline and at the end of the core treatment period (ECTP): IGF-1 < 1.3 times the upper limit of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

  • Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period [ Time Frame: Beginning of the fixed dose phase of the core treatment period and the end of the core treatment period (up to 7 months) ] [ Designated as safety issue: No ]
    Maintenance of response during the fixed dose phase of the core treatment period was defined as the percentage of participants with an insulin-like growth factor-1 (IGF-1) concentration < 1.3 times the upper limit of normal at the beginning of the fixed dose phase of the core treatment period and at the end of the core treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed.

  • Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period [ Time Frame: Beginning and the end of the extension treatment period (up to 6 months) ] [ Designated as safety issue: No ]
    Percentage of participants with the following serum insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations at the beginning (BETP) and at the end (EETP) of the extension treatment period: IGF-1 < 1.3 times the upper level of normal (ULN) and GH < 5.0 ng/mL, IGF-1 < 1.3 times ULN and GH < 1.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 5.0 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 2.5 ng/mL, IGF-1 ≤ 1.0 times ULN and GH < 1.0 ng/mL, IGF-1 < 1.3 times ULN, IGF-1 ≤ 1.0 times ULN, GH < 5.0 ng/mL, GH < 2.5 ng/mL, GH < 1.0 ng/mL, IGF-1 ≥ 1.3 times ULN and GH < 2.5 ng/mL, IGF-1 < 1.3 times ULN and GH ≥ 2.5 ng/mL, and IGF-1 ≥ 1.3 times ULN and GH ≥ 2.5 ng/mL. The growth hormone concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 hours, 2 to 4 hours post-octreotide dose. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.

  • Maintenance of Response During the Extension Treatment Period [ Time Frame: Beginning of the extension treatment period and the end of the extension treatment period (up to 13 months) ] [ Designated as safety issue: No ]
    Maintenance of an insulin-like growth factor-1 (IGF-1) response during the extension treatment period was defined as the percentage of participants with an IGF-1 concentration < 1.3 times the upper limit of normal at the beginning of the extension treatment period and at the end of the extension treatment period. IGF-1 concentration was determined in serum samples taken at the same visits growth hormone concentration was assessed.

  • Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period [ Time Frame: Baseline and the end of the extension treatment period (up to 13 months) ] [ Designated as safety issue: No ]
    The severity (absent, mild, moderate, severe) of the 5 acromegaly symptoms headache, perspiration, asthenia, swelling of extremities, and joint pain was assessed at Baseline and at the end of the extension treatment period. The percentage of participants with improved or maintained (no change) acromegaly symptoms from Baseline at the end of the extension treatment period is reported.

  • Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period [ Time Frame: Baseline and the end of the extension treatment period (up to 13 months) ] [ Designated as safety issue: No ]
    Reported is the percentage of participants who had ≥ 1, 2, or 3 of the 5 symptoms of acromegaly (headaches, perspiration, asthenia, swelling of extremities, or joint pain) of any severity (mild, moderate, or severe). This was a post hoc analysis.


Enrollment: 155
Study Start Date: March 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Octreotide capsules
Participants received octreotide capsules orally twice a day for up to 13 months. Dosing started at 40 mg per day (20 in the morning + 20 in the evening) and increased to 60 mg per day (40 in the morning + 20 in the evening) or 80 mg per day (40 in the morning + 40 in the evening) if there was inadequate IGF-1 suppression.
Drug: Octreotide capsules
Octreotide was provided in hard gelatin capsules.
Other Names:
  • MYCAPSSA™
  • Formerly known as Octreolin™

Detailed Description:

The study consisted of 2 periods, a Core Treatment Period of up to 7 months and an optional Extension Treatment Period of up to 6 months, for a total study duration of up to 13 months. The Core Treatment Period consisted of 2 phases, a Dose Escalation Phase of at least 2 months to identify the therapeutic dose for each study participant and a Fixed Dose Phase of 2 to 5 months during which the therapeutic dose was maintained.

Participants were eligible to enter the Fixed Dose Phase of the Core Treatment Period if they were clinically and biochemically controlled. The same criteria were used to allow entry into the voluntary 6-month Extension Treatment Period.

The Core Treatment Period of the study was completed if the participant had at least 2 months of treatment in the Fixed Dose Phase and a total treatment duration of at least 7 months. Participants who elected to continue into the Extension Treatment Period maintained their therapeutic dose during this period. At the end of the study (after the last dose of MYCAPSSA in either the Core Treatment Period or the Extension Treatment Period), there was a 2-week follow-up period for safety assessments.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects, aged 18 to 75 years old, inclusive.
  • Subjects with acromegaly defined as documented evidence of growth hormone-secreting pituitary tumor that is abnormally responsive to glucose, or documented elevated insulin-like growth factor-1 (IGF-1), who are currently receiving a stable dose of a somatostatin analog for at least the previous 3 months.
  • A serum IGF-1 level < 1.3 x the upper limit of normal (ULN) and a serum growth hormone (GH) level < 2.5 ng/mL.
  • Subjects able and willing to comply with the requirements of the protocol.
  • Subjects able to swallow capsules.
  • Subjects able to understand and sign written informed consent to participate in the study.

Exclusion Criteria:

  • Receiving regular injections of a somatostatin analog less frequently than once a month, ie, longer than every 4 weeks.
  • Symptomatic cholelithiasis.
  • Received pituitary radiotherapy within ten years prior to screening.
  • Undergone pituitary surgery within the prior 6 months.
  • Any condition that may jeopardize study participation.
  • Clinically significant gastrointestinal (GI), renal, or hepatic disease as determined by the Investigator.
  • Conditions (eg, bariatric surgery) significantly affecting gastric acidity or emptying.
  • Current use (within 1 month) of proton pump inhibitors (PPIs) and current chronic use of H2-antagonists.
  • Female patients who are pregnant or lactating.
  • Current or recent (< 3 months) therapy with pegvisomant.
  • Current or recent (< 2 months) therapy with cabergoline.
  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: NCT01412424

  Show 39 Study Locations
Sponsors and Collaborators
Chiasma, Inc.
Investigators
Study Chair: Shlomo Melmed, MD Cedars-Sinai Medical Center
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chiasma, Inc.
ClinicalTrials.gov Identifier: NCT01412424     History of Changes
Other Study ID Numbers: CH-ACM-01 
Study First Received: August 5, 2011
Results First Received: October 28, 2015
Last Updated: October 28, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Hungary: GYEMSZI
Israel: Ministry of Health
Italy: The Italian Medicines Agency - AIFA
Lithuania: State medicines control agency
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: CBG-NEB
Poland: The office for registration of medical products, medical devices and biocidal products
Romania: Ministry of Health
Serbia: Medicines and Medical Devices Agency of Serbia
Slovakia: SUKL
Slovenia: Public Agency for Medicinal Products and Medical Devices (JAZMP)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Chiasma, Inc.:
acromegaly
IGF-1
growth hormone
Octreolin
octreotide
somatostatin analog

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Octreotide
Somatostatin
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016