The purpose of this study is to assess the relative potency of multiple oral doses of LUM001 and SHP626 administered for 7 days as assessed by fecal bile acid excretion in overweight and obese adult subjects. This study is designed to address the relative potency question for the first time in the same.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
84
Participants will receive placebo matched to maralixibat/volixibat orally for 7 days.
Participants will receive maralixibat in 10 mg, 20 mg, 50 mg or 100 mg doses.
Participants will receive volixibat in 10 mg and 20 mg doses.
New Orleans Center for Clinical Research
Knoxville, Tennessee, United States
Change From Baseline of Fecal Bile Acid Excretion After Dosing (Day 6 and Day 7)
Fecal bile acid excretion was determined by the concentration of total bile acids in stool samples over each 24-hour collection window during the lead-in and treatment periods.
Time frame: Baseline, Day 7
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE (classified by preferred term) that occurred during the treatment period was considered a TEAE if it had a start date on or after the first dose of IMP; it had 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 the blinded IMP.
Time frame: Baseline up to follow-up (up to 16 days)
Change From Baseline in Vital Signs (Supine Pulse Rate and Standing Pulse Rate) at Day 8 / End of Treatment (ET)
Supine Pulse Rate and Standing Pulse Rate were reported.
Time frame: Baseline, Day 8
Change From Baseline in Vital Signs (Blood Pressure) at Day 8 / End of Treatment (EOT)
Supine Systolic Blood Pressure (Supine SBP); Standing Systolic Blood Pressure (Standing SBP); Supine Diastolic Blood Pressure (Supine DBP); Standing Diastolic Blood Pressure (Standing DBP) were reported.
Time frame: Baseline, Day 8
Change From Baseline in 12-lead Electrocardiogram (ECG) - Heart Rate at Day 8 / End of Treatment (EOT)
Twelve-lead ECG was performed.
Time frame: Baseline, Day 8
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Change From Baseline in 12-lead ECG Intervals at Day 8
Twelve-lead ECG was performed. The corrected QT interval (QTc) was derived by Bazett formula (QTcB=QT/(RR)\^1/2) and Fridericia formula (QTcF=QT/(RR)\^1/3). PR Interval; QRS Interval; QT Interval; QTcB Interval; QTcF Interval, RR Intervals were reported.
Time frame: Baseline, Day 8
Number of Participants with Clinically Meaningful Changes in Serum Biochemistry Laboratory Parameters
Number of participants with clinically meaningful changes in serum biochemistry laboratory parameters were reported.
Time frame: Baseline up to Day 8
Number of Participants with Clinically Meaningful Changes in Coagulation and Hematology Parameters
Activated partial thromboplastin time (aPTT), hematocrit, hemoglobin, monocytes and erythrocytes were analyzed. Number of participants with clinically meaningful change in coagulation and hematology parameters were reported.
Time frame: Baseline up to Day 8
Number of Participants With Clinically Meaningful Changes in Urinalysis Parameters
Number of participants with clinically meaningful changes in urinalysis parameters were reported.
Time frame: Baseline up to Day 8
Change From Baseline in Total Serum Bile Acid Concentration at Day 7
Serum bile acid concentrations were determined using a validated liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) method.
Time frame: Baseline, Day 7
Change From Baseline in Serum Concentration of 7- alpha-hydroxy-4-cholesten-3-one (C4) at Day 7
Serum samples were assayed for C4 using a validated LC/MS/MS method.
Time frame: Baseline, Day 7
Stool Hardness Measured by Bristol Stool Chart at Day 7
Stool hardness was assessed according to the Bristol Stool Chart, where 1 was the hardest and 7 was the softest form of stool. Types 3 and 4 were considered normal and types at either end of the scale were considered severe.
Time frame: Day 7
Frequency of Bowel Movements at Day 7
Frequency of bowel movements were calculated by treatment group and by day.
Time frame: Day 7