Safety and Efficacy of Roflumilast and Pioglitazone in Treating Adults With Nonalcoholic SteatoHepatitis

NCT01703260 | Terminated Phase 2 Results

• 2 other identifiers: ROF-NASH_205U1111-1129-5051
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the effect of roflumilast and pioglitazone therapy on serum transaminase (ALT) levels in adults with Nonalcoholic SteatoHepatitis.

Conditions

Nonalcoholic Steatohapatitis

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• Amount of Serum Alanine Transaminase (ALT) at Baseline

  Baseline

• Percent Change From Baseline in Serum ALT at Month 4

  The percent change between the serum ALT value collected at Month 4 or final visit relative to baseline.

  Month 4

Secondary Outcomes (4)

• Amount of Serum Aspartate Transaminase (AST) at Baseline

  Baseline

• Percent Change From Baseline in Serum AST at Month 4

  Month 4

• Liver Fat Content at Baseline

  Baseline

• Change From Baseline in Liver Fat Content at Month 4

  Baseline and Month 4

Study Arms (3)

Roflumilast + pioglitazone

EXPERIMENTAL

Roflumilast dose and pioglitazone dose, orally for up to 4 months

Drug: Roflumilast; Drug: Pioglitazone

Roflumilast

EXPERIMENTAL

Roflumilast dose and pioglitazone matching-placebo dose orally for up to 4 months.

Drug: Roflumilast; Drug: Placebo

Pioglitazone

EXPERIMENTAL

Pioglitazone dose, orally and roflumilast matching-placebo dose, orally for up to 4 months

Drug: Pioglitazone; Drug: Placebo

Interventions

Roflumilast DRUG

Roflumilast dose

Also known as: Daxas, Daliresp

Roflumilast; Roflumilast + pioglitazone

Pioglitazone DRUG

Pioglitazone dose

Also known as: Actos

Pioglitazone; Roflumilast + pioglitazone

Placebo DRUG

Pioglitazone placebo-matching dose

Roflumilast

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements.
• The patient or, when applicable, the patient's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a historical diagnosis of NASH, established no more than 12 months prior to study entry based on histology (liver biopsy).
• Has a NAFLD Activity Score (NAS) of ≥3, with a score of at least 1 in steatosis and lobular inflammation - the subcomponents of NAS. It is acceptable if the score for hepatocyte ballooning is "zero".
• The subject has a MRI determined liver fat fraction of equal or higher than 7 percent.
• The subject is female or male and aged 18 to 80 years, inclusive.
• A male who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 weeks after last dose.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose.
• If taking Vitamin E and/or pentoxifylline, the subject has been receiving a stable dose for 6 months prior to randomization, started Vitamin E and/or pentoxifylline therapy prior to the qualifying liver biopsy, and agrees to maintain a stable dose throughout the study when possible.
• Subject has an ALT level at Screening between 55 and 250 IU/L, inclusive, and between 60 and 250 IU/L at one other occasion during the 6 months prior to Randomization.
• If taking a statin, should be on stable dose for 6 months prior to screening.
• If taking angiotensin receptor blockers and fish oil, should be on a stable dose for at least 3 month prior to screening.
• If diabetic, the subject is on a stable dose of metformin, dipeptidyl peptidase-4 inhibitor, sulfonylurea or insulin or a combination thereof for at least 3 months prior to Screening.

You may not qualify if:

• The subject has a history of chronic liver disease other than NASH eg, chronic or acute hepatitis, Wilson's disease, alcoholic liver diseases or any other non-NASH active liver disease.
• Subjects with liver cirrhosis (of any cause) or laboratory or clinical signs of functional liver failure
• Clinically relevant abnormal laboratory values suggesting an undiagnosed disease other than NASH requiring further clinical evaluation (as assessed by the Investigator).
• The subject has active cancer or a history of a malignant disease (except basal cell carcinoma) within 5 years prior to Screening or any history of bladder cancer.
• Subject with a history of weight loss or weight gain of \>10 pounds within 6 months prior to Screening.
• Subject with a history of bariatric surgery within 5 years prior to Screening.
• The subject has received any investigational compound within 30 days prior to Screening or is currently participating in another clinical study.
• The subject has a history of hypersensitivity or allergies to roflumilast or pioglitazone including any associated excipients.
• The subject is required to take excluded medications.
• The subject has taken oral or injectable glucocorticoids for longer than 7 days within 3 months prior to Screening.
• The subject has poorly controlled Type 1 or Type 2 diabetes mellitus with an HbA1c ≥8.5 at Screening or per Investigator judgment.
• The subject has hepatitis A, B or C.
• The subject has severe immunological diseases (eg, known HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy) assessed at Screening.
• The subject had a history of diabetic gastroparesis or history of gastric bypass surgery.
• The subject had a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Unknown Facility

Coronado, California, 92118, United States

Location

Unknown Facility

Coronado, California, United States

Location

Unknown Facility

Annapolis, Maryland, 21401, United States

Location

Unknown Facility

Baltimore, Maryland, 21202, United States

Location

MeSH Terms

Interventions

Roflumilast; Pioglitazone

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

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: October 2, 2012
• First Posted: October 10, 2012
• Study Start: June 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 1, 2017
• Results First Posted: February 23, 2016

Record last verified: 2016-09

Locations

US (4)