OPTIMAL: Efficacy and Safety of Octreotide Capsules (MYCAPSSA) in Acromegaly

• Sponsor: Chiasma, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03252353
• Collaborator: (none)
• Enrollment: 56
• Locations: 60
• Arms: 2
• Anticipated Duration (Months): 56
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Octreotide capsule is a novel, orally-administered formulation of the commercially-available injectable drug octreotide. In a recent phase 3 trial, oral octreotide capsules demonstrated maintenance of biochemical response up to 13 months in the majority of patients with acromegaly previously managed with somatostatin analog injections (reference below).

Condition or Disease	Intervention/Treatment	Phase
Acromegaly	Drug: octreotide capsules; Drug: Matching placebo	Phase 3

Detailed Description

This is a double blind, randomized study that assesses the efficacy and safety of octreotide capsules vs. placebo. Eligible acromegaly patients, treated with injectable somatostatin analogs, who are biochemically controlled and have prior evidence of active disease, will be randomized to receive either octreotide capsules or placebo for up to 36 weeks. At the end of this double blind, placebo controlled period, eligible patients will receive octreotide capsules in an open-labeled extension for at least one year. Patients failing to respond (per protocol), to oral treatment, (either placebo or octreotide capsules), will be rescued with the standard of care and upon meeting the eligibility criteria could also enroll into the long term extension with octreotide capsules.

This study received agreement from the FDA, under a special protocol assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of Octreotide Capsules in Patients Who Demonstrated Biochemical Control on Injectable Somatostatin Receptor Ligands (SRL) Treatment
• Actual Study Start Date: Sep 1, 2017
• Actual Primary Completion Date: Jun 13, 2019
• Anticipated Study Completion Date: May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Octreotide capsules Octreotide capsules	Drug: octreotide capsules; octreotide capsules 40 mg/day, 60 mg/day, 80 mg/day (individual dose titration); Other Names: MYCAPSSA
Placebo Comparator: Matching Placebo Matching placebo capsules	Drug: Matching placebo; Matching placebo capsules; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period. [Week 36]

   Maintenance of response was defined by using the average IGF-1 level of the last 2 available assessments in the DPC period. If the average IGF-1 is ≤ 1×ULN, a patient was classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is > 1×ULN, a patient was classified as a non-responder. Patients who discontinue study medication during the DPC period for any reason was classified as non-responders for the primary analysis, regardless of their IGF-1 values.

Secondary Outcome Measures

1. Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period [Week 36]

   Maintenance of GH response was defined as having mean Growth Hormone (5 measurements 30 minutes apart) < 2.5 ng/mL at the end of the double blind placebo controlled period, out of those who were responders on Somatostatin Receptor Ligands (SRLs) injections at Screening.

2. Number of Patients Who Begin Rescue Treatment [Week 36]

   Number of Patients who Began Rescue Treatment Prior to and Including Week 36

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented evidence of active acromegaly

• Treatment with Somatostatin analogs injections (octreotide or lanreotide) for at least 6 months with a stable dose for at least the last three months of therapy

• Biochemically controlled

Exclusion Criteria:

• Patients taking injections of long-acting Somatostatin Receptor Ligands (SRLs) not as indicated in the label

• Pituitary surgery within six months

• Conventional or stereotactic pituitary radiotherapy any time in the past

• Patients who previously participated in CH-ACM-01 or OOC-ACM-302

• Any clinically significant uncontrolled concomitant disease

• Symptomatic cholelithiasis

• Pegvisomant, within 24 weeks

• Dopamine agonists, within 12 weeks

• Pasireotide, within 24 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck Medical Center of University of Southern California	Los Angeles	California	United States	90033
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	UCLA Medical Center	Los Angeles	California	United States	90095
4	Stanford University School of Medicine	Palo Alto	California	United States	94304
5	University of Colorado	Aurora	Colorado	United States	80045
6	The Emory Clinic	Atlanta	Georgia	United States	30322
7	John H. Stroger Jr. Hospital of Cook County	Chicago	Illinois	United States	60612
8	Johns Hopkins University Clinical Trials Unit	Baltimore	Maryland	United States	21287
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	Columbia University Medical Center	New York	New York	United States	10032
12	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	Ohio State University	Columbus	Ohio	United States	43203
15	Oregon Health and Science University	Portland	Oregon	United States	97239
16	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
17	Allegheny Endocrinology Associates	Pittsburgh	Pennsylvania	United States	15212
18	Baylor College of Medicine	Houston	Texas	United States	77030
19	Huntsman Cancer Hospital	Salt Lake City	Utah	United States	84108
20	St Vincent's Private Hospital-NSW	Darlinghurst	New South Wales	Australia	2010
21	Royal North Shore Public Hospital	St Leonards	New South Wales	Australia	2065
22	St Vincent's Hospital-VIC	Fitzroy	Victoria	Australia	3065
23	The Alfred	Melbourne	Victoria	Australia	3004
24	Melbourne Health	Parkville	Victoria	Australia	3050
25	Keogh Institute (Sir Charles Gardner)	Nedlands	Western Australia	Australia	6009
26	University Specialized Hospital for Active Treatment of Endocrinology "Acad. Iv. Pencev" EAD	Sofia		Bulgaria	1431
27	University of British Columbia	Vancouver	British Columbia	Canada	V5Z 1M9
28	St Joseph's Health Care	London	Ontario	Canada	N6A 4V2
29	McGill University Health Centre	Montreal	Quebec	Canada	H4A 3J1
30	Aarhus University Hospital	Aarhus		Denmark	8000
31	Rigshospitalet The Department of Endocrinology	Copenhagen		Denmark	2100
32	RWTH Aachen University Hospital, Medical Clinic III Division of Endocrinology and Diabetes	Aachen		Germany	52074
33	Klinikum der LMU Muenchen, Medizinische Klinik und Poliklinik IV, Endokrinologie	Munich		Germany	80336
34	Magyar Honvedseg Egeszsegugyi Kozpont, II. sz. Belgyogyaszati Osztaly	Budapest		Hungary	H-1062
35	University of Semmelweiss, Budapest	Budapest		Hungary	H-1088
36	Szegedi Tudományegyetem, I. Belgyógyászati Klinika	Szeged		Hungary	H-6720
37	Hadassah Ein-Karem Medical Center	Jerusalem		Israel	91120
38	Rabin Medical Center, Beilinson Hospital	Petah Tikva		Israel	49100
39	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
40	Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia	Monserrato		Italy	09042
41	Azienda Ospedaliero-Universitaria Pisana, Università di Pisa	Pisa		Italy	56124
42	Riga Eastern Clinical University, Hospital Gailezers Department of Endocrinology	Riga		Latvia	1038
43	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
44	Erasmus Medisch Centrum	Rotterdam		Netherlands	3015 CE
45	Dunedin Hospital	Dunedin		New Zealand	9016
46	Wellington Hospital	Wellington		New Zealand	6021
47	Katedra i Klinika Endokrynologii i Chorob Wewnetrznych	Gdansk		Poland	80-211
48	Uniwersyteckie Centrum Okulistyki i Onkologii Samodzielny Publiczny Szpital Kliniczny Slaskiego Uniwersytetu Medycznego w Katowicach, Oddzial Endokrynologii	Katowice		Poland	40-541
49	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Endokrynologii	Krakow		Poland	31-501
50	Klinika Chorob Wewnetrznych i Endokrynologii	Warszawa		Poland	02-097
51	Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami	Wroclaw		Poland	50-367
52	Medical University Centre Ljubljana	Ljubljana		Slovenia	1000
53	Sahlgrenska University Hospital	Göteborg		Sweden	SE-413 45
54	Ankara University, Faculty of Medicine	Ankara		Turkey	6100
55	Hacettepe University Medical School	Ankara		Turkey	6100
56	Ege University Medical Faculty Internal Diseases	İzmir		Turkey	35040
57	Erciyes University Medical Faculty	Kayseri		Turkey	38080
58	University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham		United Kingdom	B15 2GW
59	Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary	Manchester		United Kingdom	M13 9WL
60	Royal Victoria Infirmary	Newcastle upon Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

• Chiasma, Inc.

Investigators

• Study Chair: Susan L Samson, MD PhD, Pituitary Center at Baylor St. Luke's Medical

Study Documents (Full-Text)

• Study Protocol - Nov 29, 2017
• Statistical Analysis Plan - Nov 29, 2017

More Information

Additional Information:

• Chiasma Web Page
• Melmed et al. JCEM 2015

Publications

• 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):.
• Tuvia S, Atsmon J, Teichman SL, Katz S, Salama P, Pelled D, Landau I, Karmeli I, Bidlingmaier M, Strasburger CJ, Kleinberg DL, Melmed S, Mamluk R. Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab. 2012 Jul;97(7):2362-9. doi: 10.1210/jc.2012-1179. Epub 2012 Apr 26.

• Responsible Party: Chiasma, Inc.
• ClinicalTrials.gov Identifier: NCT03252353
• Other Study ID Numbers: OOC-ACM-303
• First Posted: Aug 17, 2017
• Last Update Posted: Nov 23, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Chiasma, Inc.: Octreotide Capsules, Acromegaly, OPTIMAL, MYCAPSSA
• Additional relevant MeSH terms: Acromegaly; Octreotide

Study Results

Participant Flow

Arm/Group Title	Octreotide Capsules	Matching Placebo
Arm/Group Description	Octreotide capsules octreotide capsules: octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration)	Matching placebo capsules Matching placebo: Matching placebo capsules
Period Title: Overall Study
STARTED	28	28
COMPLETED	28	28
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Octreotide Capsules	Matching Placebo	Total
Arm/Group Description	Octreotide capsules octreotide capsules: octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration)	Matching placebo capsules Matching placebo: Matching placebo capsules	Total of all reporting groups
Overall Participants	28	28	56
Age (years) [Mean (Standard Deviation) ]
Age	55.3 (11.97)	54.2 (10.96)	54.7 (11.38)
Sex: Female, Male (Count of Participants)
Female	16 57.1%	14 50%	30 53.6%
Male	12 42.9%	14 50%	26 46.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 10.7%	3 5.4%
Not Hispanic or Latino	28 100%	25 89.3%	53 94.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.6%	2 7.1%	3 5.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 3.6%	1 1.8%
White	27 96.4%	24 85.7%	51 91.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.6%	1 1.8%
Baseline average Insulin-like Growth Factor 1 (IGF-1) (categorical) (Count of Participants)
IGF≤ 1 Upper Limit of Normal (ULN)	27 96.4%	23 82.1%	50 89.3%
IGF > 1 to < 1.3 ULN	1 3.6%	5 17.9%	6 10.7%
IGF≥ 1.3 ULN	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period.
Description	Maintenance of response was defined by using the average IGF-1 level of the last 2 available assessments in the DPC period. If the average IGF-1 is ≤ 1×ULN, a patient was classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is > 1×ULN, a patient was classified as a non-responder. Patients who discontinue study medication during the DPC period for any reason was classified as non-responders for the primary analysis, regardless of their IGF-1 values.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

Number of Patients who Maintained Their Biochemical Response at the End of the DPC Period

Arm/Group Title	Octreotide Capsules	Matching Placebo
Arm/Group Description	Octreotide capsules octreotide capsules: octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration)	Matching placebo capsules
Measure Participants	28	28
Count of Participants [Participants]	16 57.1%	5 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Octreotide Capsules, Matching Placebo
	Comments	The proportion of [IGF-1/GH] responders was compared between treatment groups using an exact logistic regression model with categorical covariates for treatment group, prior SRL dose, and baseline [IGF-1/GH] level
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0079
	Comments
	Method	Regression, Logistic
	Comments	The adjusted proportion of responders is 58.16 for Octreotide Capsule Treatment Group vs. 19.42 for the Placebo

2. Secondary Outcome

Title	Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period
Description	Maintenance of GH response was defined as having mean Growth Hormone (5 measurements 30 minutes apart) < 2.5 ng/mL at the end of the double blind placebo controlled period, out of those who were responders on Somatostatin Receptor Ligands (SRLs) injections at Screening.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

Number of patients who maintain Growth Hormone (GH) response at the end of the double blind placebo controlled period

Arm/Group Title	Octreotide Capsules	Placebo
Arm/Group Description	Octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration)	Matching placebo
Measure Participants	28	28
Count of Participants [Participants]	21 75%	7 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Octreotide Capsules, Matching Placebo
	Comments	The proportion of [IGF-1/GH] responders was compared between treatment groups using an exact logistic regression model with categorical covariates for treatment group, prior SRL dose, and baseline [IGF-1/GH] level
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Regression, Logistic
	Comments	The adjusted proportion of responders is 77.66 for Octreotide Capsule Treatment Group vs. 30.40 for the Placebo

3. Secondary Outcome

Title	Number of Patients Who Begin Rescue Treatment
Description	Number of Patients who Began Rescue Treatment Prior to and Including Week 36
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

The number of patients who began rescue treatment

Arm/Group Title	Octreotide Capsules	Placebo
Arm/Group Description	Octreotide capsules 40 mg/day, 60 mg/day, 80 mg/day (individual dose titration)	Matching placebo
Measure Participants	28	28
Count of Participants [Participants]	7 25%	19 67.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Octreotide Capsules, Matching Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	1 year, 10 months
Adverse Event Reporting Description	Safety population: All participants enrolled in the study who received any amount of the study drug.
Arm/Group Title	Octreotide Capsules		Matching Placebo
Arm/Group Description	Octreotide capsules octreotide capsules: octreotide capsules 40mg/day, 60mg/day, 80 mg/day (individual dose titration)		Matching placebo capsules Matching placebo: Matching placebo capsules
All Cause Mortality
	Octreotide Capsules		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Octreotide Capsules		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		1/28 (3.6%)
Hepatobiliary disorders
Cholecystitis acute	1/28 (3.6%)	2	0/28 (0%)	0
Injury, poisoning and procedural complications
Joint dislocation	0/28 (0%)	0	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/28 (3.6%)	1	0/28 (0%)	0
Other (Not Including Serious) Adverse Events
	Octreotide Capsules		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/28 (100%)		27/28 (96.4%)
Gastrointestinal disorders
Abdominal discomfort	4/28 (14.3%)	4	3/28 (10.7%)	4
Abdominal pain	2/28 (7.1%)	3	2/28 (7.1%)	2
Abdominal pain upper	1/28 (3.6%)	1	3/28 (10.7%)	3
Constipation	3/28 (10.7%)	4	4/28 (14.3%)	5
Diarrhoea	8/28 (28.6%)	9	6/28 (21.4%)	6
Dyspepsia	3/28 (10.7%)	3	1/28 (3.6%)	2
Flatulence	1/28 (3.6%)	1	2/28 (7.1%)	2
Large intestinal polyp	2/28 (7.1%)	2	0/28 (0%)	0
Nausea	6/28 (21.4%)	7	3/28 (10.7%)	3
Tongue disorder	0/28 (0%)	0	2/28 (7.1%)	2
Vomiting	4/28 (14.3%)	4	0/28 (0%)	0
General disorders
Fatigue	2/28 (7.1%)	2	7/28 (25%)	8
Influenza-like illness	0/28 (0%)	0	2/28 (7.1%)	2
Oedema peripheral	2/28 (7.1%)	2	3/28 (10.7%)	3
Pain	2/28 (7.1%)	2	0/28 (0%)	0
Peripheral swelling	3/28 (10.7%)	4	4/28 (14.3%)	4
Hepatobiliary disorders
Cholelithiasis	2/28 (7.1%)	2	1/28 (3.6%)	1
Infections and infestations
Nasopharyngitis	3/28 (10.7%)	3	4/28 (14.3%)	5
Sinusitis	3/28 (10.7%)	3	0/28 (0%)	0
Upper respiratory tract infection	1/28 (3.6%)	1	2/28 (7.1%)	2
Urinary tract infection	2/28 (7.1%)	6	1/28 (3.6%)	2
Investigations
Blood glucose increased	3/28 (10.7%)	5	1/28 (3.6%)	2
Gamma-glutamyltransferase increased	1/28 (3.6%)	1	3/28 (10.7%)	4
Insulin-like growth factor increased	0/28 (0%)	0	2/28 (7.1%)	2
Weight increased	2/28 (7.1%)	2	2/28 (7.1%)	2
Metabolism and nutrition disorders
Hypercholesterolaemia	0/28 (0%)	0	2/28 (7.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	9/28 (32.1%)	11	16/28 (57.1%)	28
Arthritis	2/28 (7.1%)	3	2/28 (7.1%)	4
Back pain	2/28 (7.1%)	2	4/28 (14.3%)	5
Musculoskeletal pain	1/28 (3.6%)	1	2/28 (7.1%)	4
Osteoarthritis	3/28 (10.7%)	3	0/28 (0%)	0
Pain in extremity	0/28 (0%)	0	3/28 (10.7%)	3
Soft tissue swelling	1/28 (3.6%)	1	3/28 (10.7%)	3
Nervous system disorders
Carpal tunnel syndrome	4/28 (14.3%)	5	4/28 (14.3%)	5
Headache	4/28 (14.3%)	7	9/28 (32.1%)	17
Hypoaesthesia	0/28 (0%)	0	2/28 (7.1%)	2
Paraesthesia	0/28 (0%)	0	2/28 (7.1%)	2
Psychiatric disorders
Anxiety	1/28 (3.6%)	2	2/28 (7.1%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	6/28 (21.4%)	10	7/28 (25%)	8
Night sweats	1/28 (3.6%)	1	2/28 (7.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.