Safety and Tolerability Study of SHP626 in Overweight and Obese Adults
- Registration Number
- NCT02287779
- Lead Sponsor
- Mirum Pharmaceuticals, Inc.
- Brief Summary
This study will investigate the safety and tolerability of daily dosing regimens of SHP626 in overweight and obese adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
- 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)
- No history of alcohol or substance abuse, including use of tobacco
- No substantial changes in eating habits or exercise routine.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Three subjects per cohort will take a matched placebo SHP626 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
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel 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 \[thyroxine\]).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead) 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E) 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study 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.
- Secondary Outcome Measures
Name Time Method Average Total Fecal Bile Acid (FBA) Concentration 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.
Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration Day -1 to Day 15 Serum 7- alpha-hydroxy-4-cholesten-3-one (C4) concentrations were reported.
Maximum Observed Plasma Concentration (Cmax) of Volixibat Day 1 to Day 14 Number of Participants With Stool Hardness Using Bristol Stool Chart Day -2 to Day 14 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.
Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626) Day 1 to Day 14
Trial Locations
- Locations (1)
New Orleans Center for Clinical Research
🇺🇸Knoxville, Tennessee, United States