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

NCT01675154 | Terminated Phase 2 Results DMC

• 2 other identifiers: 3940FD-R-003940
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 1 Hyperlipoproteinemia

Keywords

hypertriglyceridemia

Outcome Measures

Primary Outcomes (4)

• Serum Triglycerides at First Intervention Period

  Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.

  4 weeks after the assigned treatment (first intervention period)

• Serum Triglycerides at Second Intervention Period

  Serum triglyceride level will be measured after taking each assigned intervention at second intervention period

  4 weeks after the assigned treatment (Second Intervention Period)

• Serum Triglycerides at Third Intervention Period

  Serum triglyceride level will be measured after taking each assigned intervention at intervention period

  4 weeks after the assigned treatment (Third Intervention Period)

• Serum Triglycerides at Fourth Intervention Period

  Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period

  4 weeks after the assigned treatment (Fourth Intervention Period)

Study Arms (4)

SLx-4090 placebo/Orlistat Placebo

PLACEBO COMPARATOR

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.

Drug: SLx-4090 placebo; Drug: Orlistat Placebo

Orlistat/placebo

EXPERIMENTAL

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.

Drug: SLx-4090 placebo; Drug: Orlistat

Orlistat placebo /SLx-4090

EXPERIMENTAL

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.

Drug: Orlistat Placebo; Drug: Slx-4090

Orlistat/SLx-4090

EXPERIMENTAL

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.

Drug: Orlistat; Drug: Slx-4090

Interventions

SLx-4090 placebo DRUG

Given for 4 weeks

Orlistat/placebo; SLx-4090 placebo/Orlistat Placebo

Orlistat Placebo DRUG

Given for 4 weeks

Orlistat placebo /SLx-4090; SLx-4090 placebo/Orlistat Placebo

Orlistat DRUG

Given for 4 weeks

Orlistat/SLx-4090; Orlistat/placebo

Slx-4090 DRUG

Given for 4 weeks

Orlistat placebo /SLx-4090; Orlistat/SLx-4090

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (2)

UT Southwestern Medical Center 5323 Harry Hines Blvd

Dallas, Texas, 75390-8537, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome; Hypertriglyceridemia

Interventions

Orlistat; 6-(4'-trifluoromethyl-6-methoxybiphenyl-2-ylcarboxamido)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid phenyl ester

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals

Limitations and Caveats

Only five patients were enrolled in the study. Two patients completed the study. One subject dropped our after Second Intervention Period. Participation of other two subjects was halted due to unavailability of study medications. Study Design: Although protocol states "This trial is randomized, double-blind cross-over trial", study design was actually not a cross over design, but adaptive/flexible design using a responsive adaptive randomization. Thus Arm/Group were not listed "per sequence".

Results Point of Contact

• Title: Dr. Abhimanyu Garg
• Organization: UT Southwestern Medical Center

abhimanyu.garg@utsouthwestern.edu

214-648-8295

Study Officials

• Abhimanyu Garg, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: 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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Model Details: This trial is adaptive design/flexible design. The participants were randomized from the start of the study

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: August 29, 2012
• Study Start: November 1, 2015
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: August 19, 2021
• Results First Posted: August 19, 2021

Record last verified: 2021-07

Locations

US (2)