Safety and Tolerability Study of SHP626 in Overweight and Obese Adults

Non-Alcoholic Steatohepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287779
• Other study ID #: SHP626-101
• Status: Completed
• Phase: Phase 1
• Start date: January 19, 2015
• Est. completion date: June 19, 2015

Study information

• Verified date: March 2019
• Source: Mirum Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the safety and tolerability of daily dosing regimens of SHP626 in overweight and obese adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: June 19, 2015
• Est. primary completion date: June 19, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-Alcoholic Steatohepatitis
• Overweight

Intervention

Drug:
• SHP626

• Placebo

Locations

Country	Name	City	State
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E)	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead)	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)	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
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study	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	Average Total Fecal Bile Acid (FBA) Concentration	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.	Day -2 up to Day 14
Secondary	Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration	Serum 7- alpha-hydroxy-4-cholesten-3-one (C4) concentrations were reported.	Day -1 to Day 15
Secondary	Number of Participants With Stool Hardness Using Bristol Stool Chart	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.	Day -2 to Day 14
Secondary	Maximum Observed Plasma Concentration (Cmax) of Volixibat		Day 1 to Day 14
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626)		Day 1 to Day 14