Safety Pilot Study of Farnesoid X Receptor (FXR) Agonist in Non-alcoholic Fatty Liver Disease (NAFLD) Patients

NCT01999101 | Completed Phase 2

• 1 other identifier: PHS-Px-104-II-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the study is to evaluate the safety and tolerability of Px-104 in NAFLD patients and to assess the influence of Px-104 on hepatic fat.

Conditions

Non Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Safety

  Analysis of clinical chemistry, hematology, and assessment of clinical signs and adverse events over 28 days. Change day 28 vs. day 1

  28 days

Secondary Outcomes (5)

• Change of hepatocellular lipid content

  day 1 and day 28

• Changes in oral glucose tolerance test (oGTT)

  baseline and day 27

• Change from baseline in fibroblast growth factor 19 (FGF-19)

  days 1, 7, 14, 21 and 28

• Change from baseline in plasma bile acid concentration

  days 1, 7, 14, 21, and 28.

• Pharmacokinetics of Px-104 and conjugates

  day 1 and day 28

Other Outcomes (2)

• Changes in the Saccharose-Lactulose-Mannitol + Sucralose (SLM+S) Test to evaluate the intestinal permeability

  baseline and day 27

• Assessment of liver steatosis by CAP-Fibroscan

  baseline and day 28

Study Arms (1)

Px-104

EXPERIMENTAL

Px-104 capsules, 5 mg

Drug: Px-104

Interventions

Px-104 DRUG

28 days treatment

Px-104

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NAFLD patients
• Weight \> 65 kg
• BMI \> 25 and \< 40
• Negative blood or urine pregnancy test (for females of childbearing potential) collected at screening followed by another negative serum pregnancy test collected within 24 hours prior to the first dose of study drug.
• Contraception: Female patients must be postmenopausal, surgically sterile, or if premenopausal, must be prepared to use at least two effective (≤1% failure rate) method of contraception during the course of the study and for 14 days after the end of dosing. Male patients with female partners of child bearing potential must be prepared to use at least two effective methods of contraception with all sexual partners unless they have had a prior vasectomy
• Must be willing and able to give written informed consent and agree to comply with the study protocol.
• Sinus rhythm in 12-lead ECG

You may not qualify if:

• Evidence of excessive alcohol, drug or substance abuse (excluding marijuana use) within 1 year of first dose.
• History or other evidence of a medical condition associated with chronic liver disease other than.
• History or other evidence of decompensated liver disease (Child-Pugh Grade B or higher), coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, hepatic encephalopathy, and bleeding from esophageal varices are conditions consistent with decompensated liver disease.
• Concomitant intake of fibrates or statins (at least 4-6 weeks before start; considering half life of medication).
• Any clinically relevant findings in ECG (identified via 24h-Holter ECG or 12-Lead ECG) at screening
• History of any structural cardiac disease.
• In addition, patients with documented or presumed unstable coronary artery disease, stable or unstable cardiovascular disease or cerebrovascular disease.
• One or more of the following conditions: (1) poorly controlled hypertension, OR (2) screening or baseline blood pressure ≥ 160 mmHg for systolic OR (3) screening or baseline blood pressure ≥ 100 mmHg for diastolic blood pressure.
• Type I or II diabetes with HbA1C \> 6.5% at screening and/or fasting plasma glucose \> 7mmol/L (\> 126 mg/dl).
• History or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy (e.g., cytomegalovirus, macular degeneration).
• Known sensibility to any ingredients contained in the investigational medicinal product (IMP)
• All conditions that do not allow magentic resonance (MR) assessments
• History of having received any investigational drug ≤ 3 months and/or 6 x half-life prior to the first dose of study drug or the expectation that such drugs will be used during the study. Patients enrolled in this study cannot be enrolled in another study for either research, diagnostic or treatment purposes.
• History of severe allergic
• Evidence of an active or suspected cancer, or a history of malignancy within the last 2 years, with the exception of patients with basal cell carcinoma that has been excised and cured.

Sponsors & Collaborators

• Phenex Pharmaceuticals AG: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Division of Gastroenterology and Hepatology, Department of Internal Medicine III

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Michael Trauner, Professor Dr med

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: December 3, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: June 1, 2016
• Last Updated: September 29, 2016

Record last verified: 2014-11

Locations

AU (1)