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

Phase 3

Completed

Conditions: Acromegaly

Interventions: Drug: Octreotide capsules

Registration Number: NCT01412424

Lead Sponsor: Chiasma, Inc.

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 155

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Octreotide capsules	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Responders at the End of the Extension Treatment Period	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.
Percentage of Responders at the End of the Core Treatment Period	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period	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.
Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period	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.
Maintenance of Response During the Extension Treatment Period	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.
Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period	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.
Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period	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.
Percentage of Participants With ≥ 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period	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.

Trial Locations

Locations (36): Military Hospital, State Health Center 2nd Department of Internal Medicine
🇭🇺
Budapest, Hungary
Instituto Nacional de Neurologia y Neurocirugía - National Institute of Neurology and Neurosurgery
🇲🇽
Mexico City, Mexico
University of Pecs
🇭🇺
Pecs, Hungary
Vilnius University Hospital Santariskiu Clinics Center of Endocrinology
🇱🇹
Vilnius, Lithuania
Semmelweiss University
🇭🇺
Budapest, Hungary
University of Szeged
🇭🇺
Szeged, Hungary
Wroclaw Medical University
🇵🇱
Wroclaw, Poland
St Bartholomew's Hospital West
🇬🇧
London, United Kingdom
Hospital of Lithuanian University of Health Sciences Kauno Klinikos
🇱🇹
Kaunas, Lithuania
Clinical Hospital of Medical University in Poznan
🇵🇱
Poznan, Poland
Servizio di Endocrinologia A.O. Spedali Civili di Brescia
🇮🇹
Brescia, Italy
Ospedale Molinette
🇮🇹
Torino, Italy
Praxis for Endocrimology and Diabetology in Oldenburg
🇩🇪
Oldenburg, Germany
Clinic for Endocrinology, Diabetes and Metabolism Diseases, Clinical Center of Serbia
🇷🇸
Belgrade, Serbia
Clinical Center of Vojvodina
🇷🇸
Novi Sad, Serbia
Department of Endocrinology and Diabetes, University Medical Centre
🇸🇮
Ljubliana, Slovenia
Campus Charité Mitte
🇩🇪
Berlin, Germany
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Medizinische Klinik Innenstadt
🇩🇪
Munich, Germany
Max Planck Institute of Psychiatry
🇩🇪
Munich, Germany
Unidad de Investigacion Clinica Cardiometabolica de Occidente
🇲🇽
Guadalajara Jalisco, Mexico
Leiden University Medical Centre
🇳🇱
Leiden, Netherlands
Erasmus University Medical Center
🇳🇱
Rotterdam, Netherlands
Dipartimento Clinico Sperimentale di Medicina e Farmacologia
🇮🇹
Messina, Italy
Centro Medico ABC
🇲🇽
Mexico D.F., Mexico
Autonomous Public Clinical Hospital No. 5
🇵🇱
Katowice, Poland
Department of Endocrinology - Jagiellonian University, Krakow
🇵🇱
Krakow, Poland
Bielanski Hospital
🇵🇱
Warsaw, Poland
County Emergency Hospital, Sf. Spiridon, Department of Endocrinology
🇷🇴
Iasi, Romania
Endocrinology Institute C.I.Parhon
🇷🇴
Bucharest, Romania
University Hospital Bratislava, Hospital of L.Derer
🇸🇰
Bratislava, Slovakia
University of Warwick - Medical School
🇬🇧
Coventry, United Kingdom
National Institute of Endocrinology and Diabetology
🇸🇰
Ľubochňa, Slovakia
The Christie Hospital NHS Trust
🇬🇧
Manchester, United Kingdom
Oxford Centre for Diabetes, Endocrinology and Metabolism
🇬🇧
Oxford, United Kingdom
ENDOC Center for Endocrine Tumors
🇩🇪
Hamburg, Germany