- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02287779
Safety and Tolerability Study of SHP626 in Overweight and Obese Adults
March 14, 2019 updated by: Mirum Pharmaceuticals, Inc.
A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Multiple Oral Doses of SHP626 in Overweight and Obese Adult Subjects
This study will investigate the safety and tolerability of daily dosing regimens of SHP626 in overweight and obese adults.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
84
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Tennessee
-
Knoxville, Tennessee, United States, 37920
- New Orleans Center for Clinical Research
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Males that comply with any applicable contraceptive requirements or females of non-childbearing potential
- No history of active or chronic disease other than that allowed by study (hypertension, hyperlipidemia and GERD or heartburn)
- Has a body mass index of 25-35 kg/m2 with a body weight of greater than 140lbs (assessed at screening)
Exclusion Criteria:
- No history of alcohol or substance abuse, including use of tobacco
- No substantial changes in eating habits or exercise routine.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SHP626
9/12 subjects -1x daily dose of 20mg for 12 days 9/12 subjects-1x daily dose of 40mg for 12 days 9/12 subjects-1x daily dose of 80mg for 12 days 9/12 subjects-1x daily dose of 120mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-1x daily dose of 160mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD) for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD; lower or higher than cohort 6) for 12 days 9/12 subjects-1x or 2x daily dose of SHP626 in an escalating titration (doses TBD).
Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days 9/12 subjects will take a 1x or 2x daily dose of SHP626 in escalating titration (doses TBD; lower or higher dose than cohort 8).
Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days
|
|
Placebo Comparator: Placebo
Three subjects per cohort will take a matched placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of investigational medicinal product (IMP) or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An adverse event (AE) that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Hematology parameters included evaluation of hemoglobin, hematocrit, red blood cells, platelets, white blood cell count; total and differential, neutrophils (absolute), eosinophils (absolute), monocytes (absolute), basophils (absolute) and lymphocytes (absolute).
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E)
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Fat soluble vitamin included vitamin A (serum retinol), vitamin D (serum 25-hydroxycholecalciferol) and vitamin E (serum alfa-tocopherol).
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Lipid panel parameters included evaluation of total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Thyroid hormone panel parameters included evaluation of thyroid hormones (TSH [thyroid stimulating hormone]; T3 [triiodothyronine] and T4 [thyroxine]).
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Coagulation included international normalized ratio, activated partial thromboplastin time and prothrombin time.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Standard chemistry parameters included evaluation of sodium, potassium, glucose, blood urea nitrogen, creatinine, calcium, chloride, thyrotropin, thyroxine, tri-iodothyronine, phosphorus, protein, bicarbonate or carbon dioxide, albumin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, urate, beta-human chorionic gonadotropin and follicle-stimulating hormone levels.
Participant with TEAE related to standard chemistry were reported with hepatic enzyme increase.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Urinalysis parameters included evaluation of pH, glucose, protein, nitrites, leukocyte esterase, occult blood, ketones, bilirubin and specific gravity levels.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Vital signs parameter included evaluation of orthostatic blood pressure, respiratory rate and body temperature.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead)
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Twelve lead electrocardiogram parameters [(heart rate (HR), PR, RR, QRS and QT intervals and information on T-wave morphology (normal/abnormal) and U-wave morphology (absent/normal or abnormal)] were assessed.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study
Time Frame: From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP.
An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
|
From the start of the study drug administration up to 9 days after the last dose of study drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Average Total Fecal Bile Acid (FBA) Concentration
Time Frame: Day -2 up to Day 14
|
Stool samples for the determination of total FBA were collected in 48-hour windows from 48 hours before dosing on Day 1 through Day 14.
The average of daily total FBA excretion is calculated before (Day -1 and Day -2) as the first pre dose of IMP and after (Day 1-12) as the first post-dose of IMP.
The FBA is calculated as Total FBA (micromoles) = FBA (micromol per liter) * weight (grams) divided by 10^3.
Participants with fecal bile acid concentration and their average pre-first dose and average post-first dose were reported.
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Day -2 up to Day 14
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Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration
Time Frame: Day -1 to Day 15
|
Serum 7- alpha-hydroxy-4-cholesten-3-one (C4) concentrations were reported.
|
Day -1 to Day 15
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Number of Participants With Stool Hardness Using Bristol Stool Chart
Time Frame: Day -2 to Day 14
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Stool hardness was assessed after each evacuation using the bristol stool chart, a medical aid designed to classify the form of human feces into 7 categories where type 1 is the hardest and type 7 is the softest.
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Day -2 to Day 14
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Maximum Observed Plasma Concentration (Cmax) of Volixibat
Time Frame: Day 1 to Day 14
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Day 1 to Day 14
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Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626)
Time Frame: Day 1 to Day 14
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Day 1 to Day 14
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 19, 2015
Primary Completion (Actual)
June 19, 2015
Study Completion (Actual)
June 19, 2015
Study Registration Dates
First Submitted
November 6, 2014
First Submitted That Met QC Criteria
November 10, 2014
First Posted (Estimate)
November 11, 2014
Study Record Updates
Last Update Posted (Actual)
March 26, 2019
Last Update Submitted That Met QC Criteria
March 14, 2019
Last Verified
March 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SHP626-101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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