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

Primary Purpose

Type 1 Hyperlipoproteinemia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SLx-4090 placebo
Orlistat Placebo
Orlistat
Slx-4090
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Hyperlipoproteinemia focused on measuring hypertriglyceridemia

Eligibility Criteria

12 Years - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UT Southwestern Medical Center 5323 Harry Hines Blvd
  • UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

SLx-4090 placebo/Orlistat Placebo

Orlistat/placebo

Orlistat placebo /SLx-4090

Orlistat/SLx-4090

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Serum Triglycerides at First Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.
Serum Triglycerides at Second Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at second intervention period
Serum Triglycerides at Third Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at intervention period
Serum Triglycerides at Fourth Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period

Secondary Outcome Measures

Full Information

First Posted
August 27, 2012
Last Updated
July 26, 2021
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01675154
Brief Title
Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
Official Title
Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
Due to unavailability of the drug.
Study Start Date
November 2015 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Hyperlipoproteinemia
Keywords
hypertriglyceridemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
This trial is adaptive design/flexible design. The participants were randomized from the start of the study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SLx-4090 placebo/Orlistat Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Orlistat/placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Orlistat placebo /SLx-4090
Arm Type
Experimental
Arm Description
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.
Arm Title
Orlistat/SLx-4090
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
SLx-4090 placebo
Intervention Description
Given for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Orlistat Placebo
Intervention Description
Given for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Orlistat
Intervention Description
Given for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Slx-4090
Intervention Description
Given for 4 weeks
Primary Outcome Measure Information:
Title
Serum Triglycerides at First Intervention Period
Description
Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.
Time Frame
4 weeks after the assigned treatment (first intervention period)
Title
Serum Triglycerides at Second Intervention Period
Description
Serum triglyceride level will be measured after taking each assigned intervention at second intervention period
Time Frame
4 weeks after the assigned treatment (Second Intervention Period)
Title
Serum Triglycerides at Third Intervention Period
Description
Serum triglyceride level will be measured after taking each assigned intervention at intervention period
Time Frame
4 weeks after the assigned treatment (Third Intervention Period)
Title
Serum Triglycerides at Fourth Intervention Period
Description
Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period
Time Frame
4 weeks after the assigned treatment (Fourth Intervention Period)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abhimanyu Garg, MD
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center 5323 Harry Hines Blvd
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8537
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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