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

• ClinicalTrials.gov Identifier: NCT01412424
• Recruitment Status: Completed
• First Posted: August 9, 2011
• Results First Posted: December 1, 2015
• Last Update Posted: August 17, 2017
• Sponsor: Chiasma, Inc.
• Information provided by (Responsible Party): Chiasma, Inc.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Acromegaly	Drug: Octreotide capsules	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 155 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Oral Octreolin™ in Patients With Acromegaly Who Are Currently Receiving Parenteral Somatostatin Analogs
• Study Start Date: March 2012
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
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™

Outcome Measures

Primary Outcome Measures :

1. Percentage of Responders at the End of the Core Treatment Period [ Time Frame: End of the core treatment period (up to 7 months) ]
   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.
2. Percentage of Responders at the End of the Extension Treatment Period [ Time Frame: End of the extension treatment period (up to 13 months) ]
   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 :

1. 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) ]
   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.
2. 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) ]
   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.
3. 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) ]
   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.
4. 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) ]
   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.
5. 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) ]
   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.
6. 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) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Germany

Campus Charité Mitte

Berlin, Germany

ENDOC Center for Endocrine Tumors

Hamburg, Germany, 20357

Medizinische Klinik Innenstadt

Munich, Germany, 80336

Max Planck Institute of Psychiatry

Munich, Germany, 80804

Praxis for Endocrimology and Diabetology in Oldenburg

Oldenburg, Germany, 26122

Hungary

Military Hospital, State Health Center 2nd Department of Internal Medicine

Budapest, Hungary, 1062

Semmelweiss University

Budapest, Hungary, 1088

University of Pecs

Pecs, Hungary, 7624

University of Szeged

Szeged, Hungary, 6720

Italy

Servizio di Endocrinologia A.O. Spedali Civili di Brescia

Brescia, Italy, 25128

Dipartimento Clinico Sperimentale di Medicina e Farmacologia

Messina, Italy, 98125

Ospedale Molinette

Torino, Italy, 10126

Lithuania

Hospital of Lithuanian University of Health Sciences Kauno Klinikos

Kaunas, Lithuania, 50009

Vilnius University Hospital Santariskiu Clinics Center of Endocrinology

Vilnius, Lithuania, 8661

Mexico

Unidad de Investigacion Clinica Cardiometabolica de Occidente

Guadalajara Jalisco, Mexico, 44150

Instituto Nacional de Neurologia y Neurocirugía - National Institute of Neurology and Neurosurgery

Mexico City, Mexico, 14269

Centro Medico ABC

Mexico D.F., Mexico, 5300

Netherlands

Leiden University Medical Centre

Leiden, Netherlands, 2333 ZA

Erasmus University Medical Center

Rotterdam, Netherlands, 3015 CE

Poland

Autonomous Public Clinical Hospital No. 5

Katowice, Poland, 40- 952

Department of Endocrinology - Jagiellonian University, Krakow

Krakow, Poland, 31-501

Clinical Hospital of Medical University in Poznan

Poznan, Poland, 60-355

Bielanski Hospital

Warsaw, Poland, 01 - 809

Wroclaw Medical University

Wroclaw, Poland, 50-367

Romania

Endocrinology Institute C.I.Parhon

Bucharest, Romania, 11863

County Emergency Hospital, Sf. Spiridon, Department of Endocrinology

Iasi, Romania, 700111

Serbia

Clinic for Endocrinology, Diabetes and Metabolism Diseases, Clinical Center of Serbia

Belgrade, Serbia, 11000

Clinical Center of Vojvodina

Novi Sad, Serbia, 21000

Slovakia

University Hospital Bratislava, Hospital of L.Derer

Bratislava, Slovakia, 833 05

National Institute of Endocrinology and Diabetology

Ľubochňa, Slovakia, 034 91

Slovenia

Department of Endocrinology and Diabetes, University Medical Centre

Ljubliana, Slovenia, 1525

United Kingdom

University of Warwick - Medical School

Coventry, United Kingdom, CV2 2DX

St Bartholomew's Hospital West

London, United Kingdom, EC1M 6BQ

The Christie Hospital NHS Trust

Manchester, United Kingdom, M13 9WL

Oxford Centre for Diabetes, Endocrinology and Metabolism

Oxford, United Kingdom, OX37LJ

Sponsors and Collaborators

Chiasma, Inc.

Investigators

• Study Chair: Shlomo Melmed, MD; Cedars-Sinai Medical Center

More Information

Additional Information:

Sponsor website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Labadzhyan A, Nachtigall LB, Fleseriu M, Gordon MB, Molitch M, Kennedy L, Samson SL, Greenman Y, Biermasz N, Bolanowski M, Haviv A, Ludlam W, Patou G, Strasburger CJ. Oral octreotide capsules for the treatment of acromegaly: comparison of 2 phase 3 trial results. Pituitary. 2021 Dec;24(6):943-953. doi: 10.1007/s11102-021-01163-2. Epub 2021 Jun 25. Erratum In: Pituitary. 2021 Aug 4;:

Melmed S, Popovic V, Bidlingmaier M, Mercado M, van der Lely AJ, Biermasz N, Bolanowski M, Coculescu M, Schopohl J, Racz K, Glaser B, Goth M, Greenman Y, Trainer P, Mezosi E, Shimon I, Giustina A, Korbonits M, Bronstein MD, Kleinberg D, Teichman S, Gliko-Kabir I, Mamluk R, Haviv A, Strasburger C. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708. doi: 10.1210/jc.2014-4113. Epub 2015 Feb 9. Erratum In: J Clin Endocrinol Metab. 2016 Oct;101(10 ):3863. J Clin Endocrinol Metab. 2020 Dec 1;105(12):

• Responsible Party: Chiasma, Inc.
• ClinicalTrials.gov Identifier: NCT01412424
• Other Study ID Numbers: CH-ACM-01
• First Posted: August 9, 2011
• Results First Posted: December 1, 2015
• Last Update Posted: August 17, 2017
• Last Verified: July 2017

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; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents