Combination Obeticholic Acid (OCA) and Statins for Monitoring of Lipids (CONTROL)
CONTROL
A Phase 2, Randomized, Double Blind, Placebo Controlled Clinical Study Investigating the Effects of Obeticholic Acid and Atorvastatin Treatment on Lipoprotein Metabolism in Subjects With Nonalcoholic Steatohepatitis
1 other identifier
interventional
84
1 country
22
Brief Summary
This Phase 2, double-blind, randomized, placebo-controlled, multicenter study, with an open-label long-term safety extension (LTSE), will evaluate the effect of Obeticholic Acid, and the subsequent addition of statin therapy, on lipoprotein metabolism in subjects with nonalcoholic steatohepatitis (NASH) with fibrosis stage 1 to 4, but no evidence of hepatic decompensation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2015
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 18, 2015
CompletedStudy Start
First participant enrolled
December 4, 2015
CompletedFirst Posted
Study publicly available on registry
December 17, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 21, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 12, 2018
CompletedResults Posted
Study results publicly available
June 4, 2018
CompletedJune 4, 2018
May 1, 2018
1.3 years
November 18, 2015
March 21, 2018
May 3, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
The Effect of Obeticholic Acid on Low-density Lipoprotein (LDL) Concentration (Least Squares Mean Change From Baseline at Week 16)
The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed nonalcoholic steatohepatitis (NASH) and the ability of atorvastatin to modulate this effect as measured by change (least squares mean) from baseline at week 16 in LDL concentration
Baseline and Week 16
The Effect of Obeticholic Acid on LDL Particle Size (Least Squares Mean Change From Baseline at Week 16)
The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed NASH and the ability of atorvastatin to modulate this effect as measured by change from baseline (least squares mean) at week 16 in LDL particle size. It is LDL particle diameter size (nm) that is reported.
Baseline and Week 16
The Effect of Obeticholic Acid on LDL Particle Concentration (Total) (Least Squares Mean Change From Baseline at Week 16)
The effect of Obeticholic Acid on LDL metabolism in subjects with biopsy confirmed nonalcoholic NASH and the ability of atorvastatin to modulate this effect as measured by change (least squares mean) from baseline at week 16 in LDL particle concentration (total)
Baseline and Week 16
Study Arms (4)
5 mg Obeticholic Acid
EXPERIMENTAL5 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg.
10 mg Obeticholic Acid
EXPERIMENTAL10 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg.
25 mg Obeticholic Acid
EXPERIMENTAL25 mg Obeticholic Acid daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg.
Placebo
PLACEBO COMPARATOROne tablet daily for the double-blind treatment period. 10 mg Atorvastatin titrating to 20mg.
Interventions
Once a day (QD) by mouth (PO)
Initiate treatment with Atorvastatin at Week 4 visit with a dose of 10 mg once daily (QD) by mouth (PO). Increase Atorvastatin to 20 mg once daily (QD) by mouth (PO) at Week 8 visit if 10 mg daily is tolerated. Atorvastatin may be titrated up or down at Week 12 visit as clinically indicated.
Eligibility Criteria
You may qualify if:
- Age ≥18 years
- Histologic evidence of NASH, as assessed by central reading of a liver biopsy obtained no more than 1 year prior to randomization, defined by the presence of all 3 key histological features of NASH with a score of at least 1 for each and a combined score of 4 or greater out of a possible 8 points according to NASH Clinical Research Network (CRN) criteria.
- Histologic evidence of fibrosis stage 1 to stage 4 (as defined by NASH CRN scoring of fibrosis) without any evidence of hepatic decompensation.
- If subject has type 2 diabetes, is on stable dose of anti-diabetic medication (except thiazolidinediones \[TZDs\]) for ≥3 months prior to Day 1.
- Is either not taking or is on stable doses of TZDs and/or Vitamin E for ≥6 months prior to Day 1.
- Contraception: Female subjects of childbearing potential must use ≥1 effective method of contraception during the study and until 30 days following the last dose of investigational product. Effective methods of contraception are considered to be the following: barrier method, ie, condom (male or female) with spermicide or diaphragm with spermicide, intrauterine device, vasectomy (partner), hormonal (eg, contraceptive pill, patch, intramuscular implant or injection), abstinence (defined as refraining from heterosexual intercourse).
- Must provide written informed consent and agree to comply with the study protocol, including adherence to protocol-described statin withdrawal and statin therapy.
You may not qualify if:
- Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening Visit 1 (significant alcohol consumption is defined as more than 2 units/day in females and more than 4 units/day in males, on average)
- Prior intolerance to treatment with atorvastatin or other 3-hydroxy-3-methyl-glutaryl (HMG) Coenzyme A reductase inhibitors (including but not limited to rhabdomyolysis).
- LDL cholesterol ≥190 mg/dL and already on statin therapy at Screening Visit 1.
- LDL cholesterol \>200 mg/dL at any Screening Visit in subjects who are not on statin therapy, or at Screening Visit 2 in statin washout subjects.
- Planned change in diet or exercise habits during participation in the double-blind period, or a significant weight change of \>5% in the prior 6 months.
- Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures.
- History of biliary diversion
- Uncontrolled diabetes defined as HbA1c ≥9.5% within 60 days prior to randomization (Day 1).
- Administration of any of the following medications as specified below:
- Prohibited 30 days prior to Day 1:
- bile acid sequestrants (BAS) including cholestyramine and its derivatives, colesevelam, colestipol, or
- omega-3 fatty acid-containing dietary supplements
- Prohibited 3 months prior to Day 1:
- nicotinic acid and derivatives, ezetimibe
- any prescription or over-the-counter (OTC) medication or herbal remedy with putative NASH efficacy (except Vitamin E or TZDs)
- +41 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
Scripps Clinic
La Jolla, California, 92037, United States
Inland Empire Liver Foundation
Rialto, California, 92377, United States
Nature Coast Clinical Research
Inverness, Florida, 34452, United States
University of Miamai, Schiff Center for Liver Diseases
Miami, Florida, 33136, United States
South Florida Center of Gastroenterology
Wellington, Florida, 33414, United States
Florida Medical Clinic, P.A.
Zephyrhills, Florida, 33542, United States
The Queen's Medical Center - Liver Center
Honolulu, Hawaii, 96813, United States
Mercy Medical Center, Institute for Digestive Health & Liver Disease
Baltimore, Maryland, 21202, United States
Kansas City Research Institute
Kansas City, Missouri, 64131, United States
St. Louis University
St Louis, Missouri, 63104, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cumberland Research Associates, LLC
Fayetteville, North Carolina, 28304, United States
Consultants for Clinical Research
Cincinnati, Ohio, 45249, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
University Gastroenterology Liver Center
Providence, Rhode Island, 02905, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
ClinSearch
Chattanooga, Tennessee, 37421, United States
Texas Clinical Research Institute, LLC
Arlington, Texas, 76012, United States
Liver Associates of Texas, P.A.
Houston, Texas, 77030, United States
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215, United States
McGuire DVAMC
Richmond, Virginia, 23249, United States
Related Publications (1)
Pockros PJ, Fuchs M, Freilich B, Schiff E, Kohli A, Lawitz EJ, Hellstern PA, Owens-Grillo J, Van Biene C, Shringarpure R, MacConell L, Shapiro D, Cohen DE. CONTROL: A randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients. Liver Int. 2019 Nov;39(11):2082-2093. doi: 10.1111/liv.14209. Epub 2019 Sep 10.
PMID: 31402538DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information
- Organization
- Intercept Pharmaceuticals, Inc
Study Officials
- STUDY DIRECTOR
David Shapiro, MD
Intercept Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2015
First Posted
December 17, 2015
Study Start
December 4, 2015
Primary Completion
March 21, 2017
Study Completion
March 12, 2018
Last Updated
June 4, 2018
Results First Posted
June 4, 2018
Record last verified: 2018-05