Safety and Tolerability Study of SHP626 in Overweight and Obese Adults

NCT02287779 | Completed Phase 1 Results

• 1 other identifier: SHP626-101
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non-Alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology

  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).

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E)

  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).

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel

  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 \[thyroxine\]).

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead)

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study

  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.

  From the start of the study drug administration up to 9 days after the last dose of study drug administration

Secondary Outcomes (5)

• Average Total Fecal Bile Acid (FBA) Concentration

  Day -2 up to Day 14

• Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration

  Day -1 to Day 15

• Number of Participants With Stool Hardness Using Bristol Stool Chart

  Day -2 to Day 14

• Maximum Observed Plasma Concentration (Cmax) of Volixibat

  Day 1 to Day 14

• Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626)

  Day 1 to Day 14

Study Arms (2)

SHP626

EXPERIMENTAL

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

PLACEBO COMPARATOR

Three subjects per cohort will take a matched placebo

Drug: Placebo

Interventions

SHP626 DRUG

SHP626

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (1)

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• Palmer M, Jennings L, Silberg DG, Bliss C, Martin P. A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis. BMC Pharmacol Toxicol. 2018 Mar 16;19(1):10. doi: 10.1186/s40360-018-0200-y.

  PMID: 29548345 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

volixibat

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Limitations and Caveats

None of the participants in the safety analysis set were included in the pharmacokinetic set because no participant had sufficient and interpretable primary pharmacokinetic data.

Results Point of Contact

• Title: Study Physician
• Organization: Mirum

medinfo@mirumpharma.com

1 650-667-4085

Study Officials

• Study Director

  Mirum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 11, 2014
• Study Start: January 19, 2015
• Primary Completion: June 19, 2015
• Study Completion: June 19, 2015
• Last Updated: March 26, 2019
• Results First Posted: December 7, 2016

Record last verified: 2019-03

Locations

US (1)