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Trial record 32 of 277 for:    Non-alcoholic Steatohepatitis | United States

Safety and Tolerability Study of SHP626 in Overweight and Obese Adults

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ClinicalTrials.gov Identifier: NCT02287779
Recruitment Status : Completed
First Posted : November 11, 2014
Results First Posted : December 7, 2016
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

Brief Summary:
This study will investigate the safety and tolerability of daily dosing regimens of SHP626 in overweight and obese adults.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Steatohepatitis Drug: SHP626 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Multiple Oral Doses of SHP626 in Overweight and Obese Adult Subjects
Actual Study Start Date : January 19, 2015
Actual Primary Completion Date : June 19, 2015
Actual Study Completion Date : June 19, 2015


Arm Intervention/treatment
Experimental: 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
Drug: SHP626
Placebo Comparator: Placebo
Three subjects per cohort will take a matched placebo
Drug: Placebo



Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology [ Time Frame: 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).

  2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E) [ Time Frame: 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).

  3. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel [ Time Frame: 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.

  4. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel [ Time Frame: 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]).

  5. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation [ Time Frame: 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.

  6. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry [ Time Frame: 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.

  7. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters [ Time Frame: 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.

  8. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs [ Time Frame: 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.

  9. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead) [ Time Frame: 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.

  10. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) [ Time Frame: 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.

  11. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study [ Time Frame: 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 :
  1. Average Total Fecal Bile Acid (FBA) Concentration [ Time Frame: 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.

  2. Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration [ Time Frame: Day -1 to Day 15 ]
    Serum 7- alpha-hydroxy-4-cholesten-3-one (C4) concentrations were reported.

  3. Number of Participants With Stool Hardness Using Bristol Stool Chart [ Time Frame: 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.

  4. Maximum Observed Plasma Concentration (Cmax) of Volixibat [ Time Frame: Day 1 to Day 14 ]
  5. Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626) [ Time Frame: Day 1 to Day 14 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • No history of alcohol or substance abuse, including use of tobacco
  • No substantial changes in eating habits or exercise routine.

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): NCT02287779


Locations
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United States, Tennessee
New Orleans Center for Clinical Research
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Mirum Pharmaceuticals, Inc.
Investigators
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Study Director: Study Director Mirum

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02287779     History of Changes
Other Study ID Numbers: SHP626-101
First Posted: November 11, 2014    Key Record Dates
Results First Posted: December 7, 2016
Last Update Posted: March 26, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Overweight
Fatty Liver
Non-alcoholic Fatty Liver Disease
Body Weight
Signs and Symptoms
Liver Diseases
Digestive System Diseases