Meta-analysis of Orlistat Laboratory Data From Placebo-controlled Clinical Trials

Roche and GSK will carry out a meta-analysis of liver function data from trials of orlistat to establish whether there is any indication of liver toxicity. The motivation is a cumulative assessment of drug-induced liver injury (DILI) conducted by the FDA following spontaneous reports of liver toxicity in people taking Xenical or Alli.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Orlistat 120; Drug: Orlistat 60

• Study Type: Observational
• Enrollment (Actual): 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All clinical trials found by search procedure:

1. In-house trial repositories at GSK and Roche
2. EMBASE (which includes MEDLINE) using the terms "orlistat", "Xenical" or "Alli", with "placebo" and "clinical trial"
3. Recently published meta-analyses found by the search will also be searched for relevant trials

Description

Inclusion Criteria:

1. The trial must be randomized and placebo-controlled
2. The orlistat dose must be 60mg or 120mg
3. Data on ALT or BIL must be available
4. The nominal treatment period must be 16 weeks or longer

Exclusion Criteria:

1. If cross-over trials are found, data from other than the first period will be excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Orlistat 120; Orlistat 120mg tid	Drug: Orlistat 120; Orlistat 120mg tid
Orlistat 60; Orlistat 60 mg tid	Drug: Orlistat 60; Orlistat 60mg tid
Placebo; No active drug	Drug: Orlistat 120; Orlistat 120mg tid; Drug: Orlistat 60; Orlistat 60mg tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Odds ratio (Orlistat120:Placebo) for subjects experiencing alanine transaminase (ALT) greater than upper limit of normal (ULN)	within one year of starting treatment
Odds ratio (Orlistat120:Placebo) for subjects experiencing total bilirubin (BIL) > ULN	within one year of starting treatment
Odds ratio (Orlistat120:Placebo) for subjects experiencing ALT > ULN for successive measurements more than two weeks apart	within one year of starting treatment
Odds ratio (Orlistat120:Placebo) for subjects experiencing BIL > ULN for successive measurements greater than two weeks apart	within one year of starting treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Odds ratio (Orlistat60:Placebo) for subjects experiencing ALT > ULN	within one year of starting treatment
Odds ratio (Orlistat60:Placebo) for subjects experiencing BIL > ULN	within one year of starting treatment
Odds ratio (Orlistat60:Placebo) for subjects experiencing ALT > ULN for successive measurements more than two weeks apart	within one year of starting treatment
Odds ratio (Orlistat60:Placebo) for subjects experiencing BIL > ULN for successive measurements greater than two weeks apart	within one year of starting treatment

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 7, 2011
• First Posted (Estimate): April 11, 2011

Study Record Updates

• Last Update Posted (Actual): June 2, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: safety; meta-analysis; orlistat; Alli; Roche; Xenical; liver-function test
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Anti-Obesity Agents; Orlistat
• Other Study ID Numbers: 114237