A Study to Investigate How the Study Drug SHP626 is Eliminated From the Body After One Dose

NCT02571192 | Completed Phase 1

• 1 other identifier: SHP626-102
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how SHP626 is absorbed and excreted from the body in healthy males.

Conditions

Non-Alcoholic Steatohepatitis

Keywords

ADME

Outcome Measures

Primary Outcomes (14)

• Pharmacokinetic parameters will be determined from the plasma and blood concentration time data of total radioactivity and from the plasma concentration-time data for SHP626 by non-compartmental analysis.

  Day 1 to day 10

• Total radioactivity (RAD) in whole blood and plasma

  Day 1 to day 10

• To determine the total RAD in urine and feces.

  Day 1 to day 10

• Maximum plasma concentration (Cmax) of 50mg [14C]-SHP626 and RAD occurring at time of maximum observed concentration (tmax)

  Day 1 to day 10

• Area under the plasma concentration curve (AUC0-t) of 50mg [14C]-SHP626 and RAD from the time of dosing to the last measurable concentration

  Day 1 to Day 10

• Area under the plasma concentration curve (AUC0-∞ ) of 50mg [14C]-SHP626 and RAD extrapolated to infinity, calculated using the observed value of the last non-zero plasma concentration

  Day 1 to Day 10

• First order rate constant associated with the terminal portion of the plasma curve terminal half-life (t½) for 50mg [14C]-SHP626 and RAD

  Day 1 to Day 10

• Total body clearance (CL/F ) of 50mg [14C]-SHP626 and RAD for extravascular administration divided by the fraction of dose absorbed

  Day 1-10

• Volume of distribution (Vz/F ) of 50mg [14C]-SHP626 and RAD associated with the terminal slope following extra-vascular administration divided by the fraction of dose absorbed

  Day 1-10

• Cumulative amount (Aef )of RAD recovered in stool over the dosing interval

  Day 1-10

• Excreted Percent of RAD recovered in stool over the dosing interval

  Day 1-10

• Cumulative amount (Aeu ) of RAD recovered in urine over the dosing interval

  Day 1-10

• Excreted Percent of RAD recovered in urine over the dosing interval

  Day 1-10

• Renal Clearance (CLR ) of 50mg [14C]-SHP626

  Day 1 -10

Secondary Outcomes (10)

• Characterize and identify metabolites of [14C]-SHP626 in plasma by accelerator mass spectrometry for radioactivity quantification

  Day 1 to day 10

• Characterize and identify metabolites of [14C]-SHP626 in urine by accelerator mass spectrometry for radioactivity quantification

  Day 1 to day 10

• Characterize and identify metabolites of [14C]-SHP626 in feces by liquid scintillation counting

  Day 1 to day 10

• Assess the safety and tolerability of [14C]-SHP626 by adverse events (AEs) defined as changes, including changes from baseline in physical examination findings

  Screening to day 7

• Changes from baseline in vital signs

  Screening to day 7

Study Arms (1)

Experimental Drug

EXPERIMENTAL

single oral dose radiolabelled 50mg of SHP626

Drug: SHP626; Radiation: 5.95 μCi RAD

Interventions

SHP626 DRUG

single oral dose 50mg SHP626 with approximately 5.95 μCi RAD

Experimental Drug

5.95 μCi RAD RADIATION

Experimental Drug

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 50 years, inclusive, at the time of consent.
• Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, thyroid panel (includes T3, T4 and TSH at Screening only), blood chemistry, coagulation and urinalysis
• Must have a body mass index between 18.0-30.0kg/m² inclusive with a body weight \>50 kg (110 lbs).
• Ability to swallow all investigational product.
• A minimum of 1 bowel movement per day.

You may not qualify if:

• History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gallbladder removal, gastric bypass surgery, ileal resection, any small intestinal resection,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.
• Known or suspected intolerance or hypersensitivity to the investigational product, or closely-related compounds, or any of the stated ingredients.
• Significant illness, as judged by the investigator, within 2 weeks of the 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 the dose of investigational product.
• Within 30 days prior to the 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, as assessed by the investigator.
• Confirmed systolic blood pressure \>139mmHg or \<89mmHg, and diastolic blood pressure \>89mmHg or \<49mmHg.
• Twelve-lead ECG demonstrating QTc \>450 msec at screening. If QTc exceeds 450msec, 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 a positive screen for alcohol or drugs of abuse at Check-in (Day -1).
• Male subjects who consume more than 21 units of alcohol per week or 3 units of alcohol per day.
• A positive human immunodeficiency virus antibody screen, hepatitis B surface antigen, or hepatitis C virus antibody screen.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance Madison Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Related Publications (1)

• Siebers N, Palmer M, Silberg DG, Jennings L, Bliss C, Martin PT. Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy Men: Phase 1 Open-Label Study. Eur J Drug Metab Pharmacokinet. 2018 Feb;43(1):91-101. doi: 10.1007/s13318-017-0429-7.

  PMID: 28702877 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

volixibat

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Nicholas Siebers, MD

  Covance Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 8, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 1, 2019

Record last verified: 2019-04

Locations

US (1)