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| ID | Type | Description | Link |
|---|---|---|---|
| FD-R-003940 |
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Due to unavailability of the drug.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SLx-4090 placebo | Drug | Given for 4 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Abhimanyu Garg, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern Medical Center 5323 Harry Hines Blvd | Dallas | Texas | 75390-8537 | United States | ||
| UT Southwestern Medical Center |
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This trial is adaptive design/flexible design. The participants were randomized from the start of the study
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| ID | Title | Description |
|---|---|---|
| FG000 | SLx-4090 Placebo/Orlistat Placebo First | First, 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. SLx-4090 placebo: Given for 4 weeks Orlistat Placebo: Given for 4 weeks |
| FG001 | Orlistat/SLx-4090 Placebo | Then, Orlistat two capsules 60 mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50 mg each, three times per day with meals were administered SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks |
| FG002 | Orlistat Placebo /SLx-4090 | Then, Orlistat placebo 2 capsules, 60 mg each three times per day with meals. SLx-4090 4 tablets, 50 mg each. three times per day with meals were administered Orlistat Placebo: Given for 4 weeks SLx-4090: Given for 4 weeks |
| FG003 | Orlistat/SLx-4090 | Then, Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50 mg each, three times per day with meals were administered Orlistat: Given for 4 weeks SLx-4090: Given for 4 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention Period (4 Weeks) |
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| First Washout Period (1 Week) |
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| Second Intervention Period (4 Weeks) |
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| Second Washout Period (1 Week) |
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| Third Intervention Period (4 Weeks) |
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| Third Washout Period (1 Week) |
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| Fourth Intervention Period (4 Weeks) |
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The baseline characteristics are based on first intervention period assignment. This trial is an adaptive design/flexible design using responsive adaptive randomization. The participants were randomized from the start of the study
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/Placebo at First Intervention Period | 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. |
| BG001 | Orlistat/Placebo at First Intervention Period |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum Triglycerides at First Intervention Period | Serum triglyceride level will be measured after taking each assigned intervention at first intervention period. | 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. | Posted | Mean | Standard Deviation | mg/dL | 4 weeks after the assigned treatment (first intervention period) |
|
Over a period of 1 year .
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.
Includes all participants who started first, second, third and fourth intervention periods. Events were collected separately for each period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1st Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat Placebo: Given for 4 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancreatitis. | Endocrine disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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".
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Abhimanyu Garg | UT Southwestern Medical Center | 214-648-8295 | abhimanyu.garg@utsouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 28, 2018 | May 18, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C538489 | Familial hyperchylomicronemia syndrome |
| D015228 | Hypertriglyceridemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077403 | Orlistat |
| C559489 | 6-(4'-trifluoromethyl-6-methoxybiphenyl-2-ylcarboxamido)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid phenyl ester |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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This trial is adaptive design/flexible design. The participants were randomized from the start of the study
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| Orlistat Placebo | Drug | Given for 4 weeks |
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| Orlistat | Drug | Given for 4 weeks |
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| Slx-4090 | Drug | Given for 4 weeks |
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| Dallas |
| Texas |
| 75390 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED | One patient dropped out during Period 3 due to personal reasons. Therefore, not included in this intervention period. |
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| NOT COMPLETED |
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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 were administered. |
| BG002 | Orlistat Placebo /Slx-4090 at First Intervention Period | Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals were administered |
| BG003 | Orlistat/SLx-4090 at First Intervention Period | Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals were administered. |
| BG004 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| BMI | Number | participants |
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| Triglycerides | Mean | Standard Deviation | mg/dL |
|
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. SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks |
| OG002 | 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. Orlistat Placebo: Given for 4 weeks Slx-4090: Given for 4 weeks |
| OG003 | 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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks |
|
|
| Primary | Serum Triglycerides at Second Intervention Period | Serum triglyceride level will be measured after taking each assigned intervention at second intervention period | Patient assigned to SLX-4090 placebo/Orlistat placebo group withdrew from the study in this phase. One more subject was assigned to the Orlistat/SLx-4090 but could not start the study as the drug SLx-4090 was not available. 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. | Posted | Mean | Standard Deviation | mg/dL | 4 weeks after the assigned treatment (Second Intervention Period) |
|
|
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| Primary | Serum Triglycerides at Third Intervention Period | Serum triglyceride level will be measured after taking each assigned intervention at intervention period | Patient assigned to Orlistat/SLX-4090 placebo group did not start the assigned treatment due to lack of drugs. 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. | Posted | Mean | Standard Deviation | mg/dL | 4 weeks after the assigned treatment (Third Intervention Period) |
|
|
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| Primary | Serum Triglycerides at Fourth Intervention Period | Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period | Patient assigned to Orlistat/SLX-4090 group did not start the assigned treatment due to lack of drugs. 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. | Posted | Mean | Standard Deviation | mg/dL | 4 weeks after the assigned treatment (Fourth Intervention Period) |
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|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 0 |
| 2 |
| EG001 | 1st Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | 1st Intervention Period: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. Orlistat Placebo: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 1 | 0 | 1 | 1 | 1 |
| EG003 | 1st Intervention Period: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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 1 | 0 | 1 | 1 | 1 |
| EG004 | 2nd Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat Placebo: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG005 | 2nd Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG006 | 2nd Intervention Period:Orlistat Placebo /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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 1 | 0 | 1 | 1 | 1 |
| EG007 | 2nd Intervention Period: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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 2 | 1 | 2 | 0 | 2 |
| EG008 | 3rd Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat Placebo: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG009 | 3rd Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG010 | 3rd Intervention Period:Orlistat Placebo /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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG011 | 3rd Intervention Period: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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 0 | 0 | 0 | 0 | 0 |
| EG012 | 4th Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat Placebo: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG013 | 4th Intervention Period: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. SLx-4090 placebo: Given for 4 weeks Orlistat: Given for 4 weeks | 0 | 0 | 0 | 0 | 0 | 0 |
| EG014 | 4th Intervention Period:Orlistat Placebo /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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 1 | 0 | 1 | 0 | 1 |
| EG015 | 4th Intervention Period: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. Orlistat: Given for 4 weeks Slx-4090: Given for 4 weeks | 0 | 0 | 0 | 0 | 0 | 0 |
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Increased urgency of passing stool | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
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| D009750 |
| Nutritional and Metabolic Diseases |