Study to Assess the Relative Potency of Multiple Oral Doses of LUM001 and SHP626 in Overweight and Obese Adults as Assessed by Fecal Bile Acid Excretion

NCT02475317 | Completed Phase 1

• 1 other identifier: SHP625-101
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Volunteer

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Day 7

Secondary Outcomes (12)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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)

  Baseline, Day 8

• Change From Baseline in Vital Signs (Blood Pressure) at Day 8 / End of Treatment (EOT)

  Baseline, Day 8

• Change From Baseline in 12-lead Electrocardiogram (ECG) - Heart Rate at Day 8 / End of Treatment (EOT)

  Baseline, Day 8

• Change From Baseline in 12-lead ECG Intervals at Day 8

  Baseline, Day 8

Study Arms (8)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to maralixibat 10 milligram (mg), 20 mg, 50 mg once daily (QD), 50 mg twice daily (BID), 100 mg liquid formulation and volixibat 10 mg, 20 mg capsule orally for 7 days.

Drug: Placebo

Maralixibat 10mg

EXPERIMENTAL

Participants will receive maralixibat 10 mg liquid formulation orally QD for 7 days.

Drug: Maralixibat

Volixibat 10mg

EXPERIMENTAL

Participants will receive volixibat 10 mg capsule orally QD for 7 days.

Drug: Volixibat

Maralixibat 20mg

EXPERIMENTAL

Participants will receive maralixibat 20 mg liquid formulation orally QD for 7 days.

Drug: Maralixibat

Volixibat 20mg

EXPERIMENTAL

Participants will receive volixibat 20 mg capsule orally QD for 7 days.

Drug: Volixibat

Maralixibat 50mg

EXPERIMENTAL

Participants will receive maralixibat 50 mg liquid formulation orally QD for 7 days.

Drug: Maralixibat

Maralixibat 50mg BID

EXPERIMENTAL

Participants will receive maralixibat 50 mg liquid formulation orally BID for 7 days.

Drug: Maralixibat

Maralixibat 100mg

EXPERIMENTAL

Participants will receive maralixibat 100 mg liquid formulation orally QD for 7 days.

Drug: Maralixibat

Interventions

Placebo DRUG

Participants will receive placebo matched to maralixibat/volixibat orally for 7 days.

Placebo

Maralixibat DRUG

Participants will receive maralixibat in 10 mg, 20 mg, 50 mg or 100 mg doses.

Also known as: LUM001

Maralixibat 100mg; Maralixibat 10mg; Maralixibat 20mg; Maralixibat 50mg; Maralixibat 50mg BID

Volixibat DRUG

Participants will receive volixibat in 10 mg and 20 mg doses.

Also known as: SHP626

Volixibat 10mg; Volixibat 20mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An understanding, ability, and willingness to fully comply with study procedures, study diet, and restrictions.
• Ability to voluntarily provide written, signed, and dated (personally or via a legally-authorized representative) informed consent/and assent as applicable to participate in the study.
• Males who agree to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential (see Section 4.4 for details).
• Must be considered generally healthy. Health status is defined by the absence of evidence of any active or chronic disease (see Section 7.2.2.1 for details and exceptions) following the completion of a detailed medical and surgical history, a complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
• All clinical laboratory parameters are within normal laboratory limit or not found to be clinically significant by the principal investigator.
• Ability to swallow a dose(s) of investigational product(s).

You may not qualify if:

• History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological, or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
• Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
• Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
• Significant illness, as judged by the investigator, within 2 weeks prior to the first dose of investigational product.
• Known history of alcohol or other substance abuse within the last year.
• Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
• Within 30 days prior to the first dose of investigational product:
• Have used an investigational product (if elimination half-life is \<6 days, otherwise 5 half-lives).
• Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
• Have had any substantial changes in eating habits or exercise routine, as assessed by the investigator
• Confirmed resting systolic blood pressure \>145 mmHg or \<89 mmHg, and diastolic blood pressure \>95 mmHg or \<59 mmHg.
• Twelve-lead ECG demonstrating QTc \>460 milliseconds for male subjects or \>470 milliseconds for female subjects at screening. If QTc exceeds 460 milliseconds for males or 470 milliseconds for females, the ECG should be repeated 2 more times and the average of the 3 QTc values should be used to determine the subject's eligibility
• A positive screen for drugs of abuse at screening or at Day -3 (check-in).
• Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit=1 beer or 1 wine \[5 oz/150 mL\] or 1 liquor \[1.5 oz/40 mL\] or 0.75 oz alcohol).
• A positive HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (1)

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Location

MeSH Terms

Interventions

maralixibat; volixibat

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 18, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 4, 2019

Record last verified: 2019-04

Locations

US (1)