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

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ClinicalTrials.gov Identifier: NCT02571192
Recruitment Status : Completed
First Posted : October 8, 2015
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Non-Alcoholic Steatohepatitis Drug: SHP626 Radiation: 5.95 μCi RAD Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1, Open-label Study to Investigate the Absorption, Distribution, Metabolism, and Excretion of [14C]-SHP626 Following a Single Oral Dose in Healthy Male Subjects
Study Start Date : October 1, 2015
Actual Primary Completion Date : October 1, 2015
Actual Study Completion Date : October 1, 2015


Arm Intervention/treatment
Experimental: Experimental Drug
single oral dose radiolabelled 50mg of SHP626
Drug: SHP626
single oral dose 50mg SHP626 with approximately 5.95 μCi RAD

Radiation: 5.95 μCi RAD



Primary Outcome Measures :
  1. 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. [ Time Frame: Day 1 to day 10 ]
  2. Total radioactivity (RAD) in whole blood and plasma [ Time Frame: Day 1 to day 10 ]
  3. To determine the total RAD in urine and feces. [ Time Frame: Day 1 to day 10 ]
  4. Maximum plasma concentration (Cmax) of 50mg [14C]-SHP626 and RAD occurring at time of maximum observed concentration (tmax) [ Time Frame: Day 1 to day 10 ]
  5. Area under the plasma concentration curve (AUC0-t) of 50mg [14C]-SHP626 and RAD from the time of dosing to the last measurable concentration [ Time Frame: Day 1 to Day 10 ]
  6. 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 [ Time Frame: Day 1 to Day 10 ]
  7. First order rate constant associated with the terminal portion of the plasma curve terminal half-life (t½) for 50mg [14C]-SHP626 and RAD [ Time Frame: Day 1 to Day 10 ]
  8. Total body clearance (CL/F ) of 50mg [14C]-SHP626 and RAD for extravascular administration divided by the fraction of dose absorbed [ Time Frame: Day 1-10 ]
  9. 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 [ Time Frame: Day 1-10 ]
  10. Cumulative amount (Aef )of RAD recovered in stool over the dosing interval [ Time Frame: Day 1-10 ]
  11. Excreted Percent of RAD recovered in stool over the dosing interval [ Time Frame: Day 1-10 ]
  12. Cumulative amount (Aeu ) of RAD recovered in urine over the dosing interval [ Time Frame: Day 1-10 ]
  13. Excreted Percent of RAD recovered in urine over the dosing interval [ Time Frame: Day 1-10 ]
  14. Renal Clearance (CLR ) of 50mg [14C]-SHP626 [ Time Frame: Day 1 -10 ]

Secondary Outcome Measures :
  1. Characterize and identify metabolites of [14C]-SHP626 in plasma by accelerator mass spectrometry for radioactivity quantification [ Time Frame: Day 1 to day 10 ]
    Metabolites in the excreta and/or plasma will then be structurally identified by a combination of techniques such as co-chromatography with authentic reference standards, high performance liquid chromatography-mass spectrometry, and other spectroscopic techniques if necessary

  2. Characterize and identify metabolites of [14C]-SHP626 in urine by accelerator mass spectrometry for radioactivity quantification [ Time Frame: Day 1 to day 10 ]
    Metabolites in the excreta and/or plasma will then be structurally identified by a combination of techniques such as co-chromatography with authentic reference standards, high performance liquid chromatography-mass spectrometry, and other spectroscopic techniques if necessary

  3. Characterize and identify metabolites of [14C]-SHP626 in feces by liquid scintillation counting [ Time Frame: Day 1 to day 10 ]
    Metabolites in the excreta and/or plasma will then be structurally identified by a combination of techniques such as co-chromatography with authentic reference standards, high performance liquid chromatography-mass spectrometry, and other spectroscopic techniques if necessary

  4. Assess the safety and tolerability of [14C]-SHP626 by adverse events (AEs) defined as changes, including changes from baseline in physical examination findings [ Time Frame: Screening to day 7 ]
    AEs will be coded using the agreed upon version of MedDRA. The number of events, incidence, and percentage of TEAEs will be calculated overall, by system organ class and by preferred term. TEAEs will be further summarized by severity and relationship to investigational product. AEs related to investigational product, AEs leading to withdrawal, SAEs, and deaths will be similarly summarized/listed.

  5. Changes from baseline in vital signs [ Time Frame: Screening to day 7 ]
  6. Changes from baseline in ECGs [ Time Frame: Screening to day 7 ]
  7. Changes from baseline in hematology [ Time Frame: Screening to day 7 ]
  8. Changes from baseline in coagulation [ Time Frame: Screening to day 7 ]
  9. Changes in baseline in urinalysis [ Time Frame: Screening to day 7 ]
  10. Changes in baseline in chemistry [ Time Frame: Screening to day 7 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age between 18 and 50 years, inclusive, at the time of consent.
  2. 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
  3. Must have a body mass index between 18.0-30.0kg/m² inclusive with a body weight >50 kg (110 lbs).
  4. Ability to swallow all investigational product.
  5. A minimum of 1 bowel movement per day.

Exclusion Criteria:

  1. 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.
  2. Current or relevant history of physical or psychiatric illness.
  3. Known or suspected intolerance or hypersensitivity to the investigational product, or closely-related compounds, or any of the stated ingredients.
  4. Significant illness, as judged by the investigator, within 2 weeks of the dose of investigational product.
  5. Known history of alcohol or other substance abuse within the last year.
  6. Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to the dose of investigational product.
  7. 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.
  8. Confirmed systolic blood pressure >139mmHg or <89mmHg, and diastolic blood pressure >89mmHg or <49mmHg.
  9. 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.
  10. A positive screen for drugs of abuse at Screening or a positive screen for alcohol or drugs of abuse at Check-in (Day -1).
  11. Male subjects who consume more than 21 units of alcohol per week or 3 units of alcohol per day.
  12. A positive human immunodeficiency virus antibody screen, hepatitis B surface antigen, or hepatitis C virus antibody screen.
  13. Use of tobacco in any form
  14. Routine consumption of more than 2 units of caffeine per day
  15. Current use of any medication including over-the-counter, herbal, or homeopathic preparations
  16. An inability to follow a standardized diet and meal schedule or inability to fast
  17. Have participated in a [14C]-study within the last 6 months prior to the dose of investigational product.
  18. Exposure to clinically significant radiation within 12 months prior to the dose of investigational product

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02571192


Locations
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United States, Wisconsin
Covance Madison Clinical Research Unit
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
Mirum Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Nicholas Siebers, MD Covance Clinical Pharmacology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02571192     History of Changes
Other Study ID Numbers: SHP626-102
First Posted: October 8, 2015    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Keywords provided by Mirum Pharmaceuticals, Inc.:
ADME
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases