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

Acromegaly Clinical Trial

Official title:

Efficacy and Safety of Oral Octreolin™ in Patients With Acromegaly Who Are Currently Receiving Parenteral Somatostatin Analogs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01412424
• Other study ID #: CH-ACM-01
• Status: Completed
• Phase: Phase 3
• First received: August 5, 2011
• Last updated: October 28, 2015
• Start date: March 2012
• Est. completion date: May 2014

Study information

• Verified date: October 2015
• Source: Chiasma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesHungary: GYEMSZIIsrael: Ministry of HealthItaly: The Italian Medicines Agency - AIFALithuania: State medicines control agencyMexico: Federal Commission for Protection Against Health RisksNetherlands: CBG-NEBPoland: The office for registration of medical products, medical devices and biocidal productsRomania: Ministry of HealthSerbia: Medicines and Medical Devices Agency of SerbiaSlovakia: SUKLSlovenia: Public Agency for Medicinal Products and Medical Devices (JAZMP)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• Octreotide capsules
Octreotide was provided in hard gelatin capsules.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Chiasma, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Israel,  Italy,  Lithuania,  Mexico,  Netherlands,  Poland,  Romania,  Serbia,  Slovakia,  Slovenia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Responders at the End of the Core Treatment Period	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.	End of the core treatment period (up to 7 months)	No
Primary	Percentage of Responders at the End of the Extension Treatment Period	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.	End of the extension treatment period (up to 13 months)	No
Secondary	Percentage of Participants With Specified IGF-1 and GH Concentrations at Baseline and at the End of the Core Treatment Period	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.	Baseline and the end of the core treatment period (up to 7 months)	No
Secondary	Maintenance of Response During the Fixed Dose Phase of the Core Treatment Period	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.	Beginning of the fixed dose phase of the core treatment period and the end of the core treatment period (up to 7 months)	No
Secondary	Percentage of Participants With Specified IGF-1 and GH Concentrations at the Beginning and at the End of the Extension Treatment Period	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.	Beginning and the end of the extension treatment period (up to 6 months)	No
Secondary	Maintenance of Response During the Extension Treatment Period	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.	Beginning of the extension treatment period and the end of the extension treatment period (up to 13 months)	No
Secondary	Percentage of Participants With Improved or Maintained Acromegaly Symptoms at the End of the Extension Treatment Period	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.	Baseline and the end of the extension treatment period (up to 13 months)	No
Secondary	Percentage of Participants With = 1, 2, or 3 Acromegaly Symptoms at Baseline and at the End of the Extension Treatment Period	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.	Baseline and the end of the extension treatment period (up to 13 months)	No

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