Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia

NCT ID: NCT01675154

Last Updated: 2021-08-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2020-06-30

Brief Summary

Funding Source - FDA OOPD

This study is being done to find out whether an investigational (not approved by FDA ) drug called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in combination can treat the high blood fat (elevated triglycerides)levels found in the condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone, the current standard medical care.

It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The researchers are interested in learning whether any one of these drugs when given alone or in combination is more effective and safe in treating T1HLP.

Detailed Description

Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related proteins. Treatment of these patients is challenging as triglyceride-lowering medications are ineffective. A low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. Therefore, we wish to investigate whether inducing dietary fat malabsorption or inhibiting chylomicron formation will cause further lowering of serum triglycerides (TG) beyond the effect of limiting dietary fat intake.

We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20 patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of four weeks followed by a one week wash out period. During the last week of each study period, fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl palmitate levels during a meal tolerance test. Repeated measures analysis of variance will be used for statistical comparisons.

Our results may help in designing novel therapeutic approaches for patients with Type 1 hyperlipoproteinemia.

Conditions

Type 1 Hyperlipoproteinemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SLx-4090 placebo/Orlistat Placebo

Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.

Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.

This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.

Group Type: PLACEBO_COMPARATOR

SLx-4090 placebo

Intervention Type: DRUG

Given for 4 weeks

Orlistat Placebo

Intervention Type: DRUG

Given for 4 weeks

Orlistat/placebo

Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.

Group Type: EXPERIMENTAL

SLx-4090 placebo

Intervention Type: DRUG

Given for 4 weeks

Orlistat

Intervention Type: DRUG

Given for 4 weeks

Orlistat placebo /SLx-4090

Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.

Group Type: EXPERIMENTAL

Orlistat Placebo

Intervention Type: DRUG

Given for 4 weeks

Slx-4090

Intervention Type: DRUG

Given for 4 weeks

Orlistat/SLx-4090

Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment.

Group Type: EXPERIMENTAL

Orlistat

Intervention Type: DRUG

Given for 4 weeks

Slx-4090

Intervention Type: DRUG

Given for 4 weeks

Interventions

SLx-4090 placebo

Given for 4 weeks

Intervention Type: DRUG

Orlistat Placebo

Given for 4 weeks

Intervention Type: DRUG

Orlistat

Given for 4 weeks

Intervention Type: DRUG

Slx-4090

Given for 4 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type I hyperlipoproteinemia.
• Fasting serum triglyceride levels of greater than 1000 mg/dL.
• Age > 12 years

Exclusion Criteria

• Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-protease inhibitors, retinoic acid derivatives and interferons.
• Pregnant or lactating women
• Significant liver disease (elevated transaminases > 2 times upper limit of normal)
• Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks for men or 168 g per week for men)
• Drug use (cocaine, marijuana, LSD, etc.)
• Major surgery in the past three months
• Congestive heart failure
• Serum creatinine greater than 2.5 mg/dL
• Cancer within the past five years
• Gastrointestinal surgery in the past
• Current therapy with anti-coagulants, digoxin and anti-arrhythmics
• Chronic malabsorption syndromes
• Cholestasis
• Acute illnesses such as acute pancreatitis in the last 8 weeks

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Abhimanyu Garg

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abhimanyu Garg, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center 5323 Harry Hines Blvd

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

FD-R-003940

Identifier Type: -

Identifier Source: secondary_id

3940

Identifier Type: -

Identifier Source: org_study_id