Multiple Ascending Oral Dose Phase I Study With Px-102

NCT01998672 | Completed Phase 1

• 1 other identifier: PHS-Px-102-I-02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and tolerability of the FXR agonist Px-102 in healthy subjects after 7 days multiple oral dosing.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of Px-102

  Adverse event monitoring, laboratory values, cardiovascular monitoring. Comparison active vs. placebo

  7 days

Secondary Outcomes (2)

• Pharmacokinetics of Px-102 and metabolites

  Day 1: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h; Day 5 and 6: pre-dose; Day 7: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h, 30 h.

• Pharmacodynamics

  Pre-dose, 1, 2, 4, 8 and 10 hours after administration on Days 1 and 7; Pre-dose, 2 hours and 8 hours after administration on Days 2 to 6; at 22 hours after the last administration

Study Arms (2)

Px-102

ACTIVE COMPARATOR

Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg

Drug: Px-102

Placebo

PLACEBO COMPARATOR

Oral drinking solution

Drug: Placebo

Interventions

Px-102 DRUG

Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg

Px-102

Placebo DRUG

Drinking solution

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subject of Caucasian origin 18 to 45 years of age (inclusive).
• Good state of health (mentally and physically) as determined by medical history, physical examination, vital signs, ECG recording and clinical lab results.
• BMI in between 20-29 kg/m² (inclusive); with absolute weight in between 70 to 120 kg.
• Total cholesterol and liver enzyme levels \[alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP)\] strictly within the normal ranges at screening and on Day -1. Serum triglyceride not exceeding the upper limit of normal range.
• HbA1c ≤ 6.5%
• Subject has been informed both verbally and in writing and has given written consent to participation in the study prior to start and any study-related procedure.
• Negative results for HIV- and Hepatitis-B and -C serology at screening.
• Subject (including female partners of childbearing potential) has to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly), e.g. implants, injectables, combined oral contra-ceptives in combination with a barrier method, some intrauterine contraceptive devices or sexual abstinence.

You may not qualify if:

• Female gender
• Use of prescription or non-prescription drugs within 7 days (30 if the drug is a possible enzyme inducer) prior to administration of study medication. Use of drugs known to induce steatosis (e.g. valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism
• Any acute or chronic illness or clinically relevant finding at screening and at base-line examination which may jeopardize the subject's participation in the study
• History or presence of biliary obstruction or biliary disease, hepatic encephalopathy, advanced ascites, portal hypertension, esophageal/gastric variceal bleeding, hepatocellular carcinoma, previous liver transplantation or any other chronic liver disease
• Renal dysfunction, e.g. glomerular filtration rate ≤ 80 ml/min/1.73 m2 (as determined by the formula of Cockroft-Gault)
• Type I or II Diabetes
• Any clinically relevant abnormality on screening medical assessment, laboratory examination, 12-lead ECG
• Any clinically relevant finding in the baseline telemetry within the pre-dose evaluated observation period of at least 20 hours
• Marked baseline prolongation of QT/QTc interval (QTc interval \> 440 ms) in the 12-lead ECG using the Fridericia method for QTc analysis
• Heart rate \< 50 bpm.
• History of pathological cardiovascular symptoms or a severe cardiovascular event
• History of severe chronic autoimmune diseases such as severe allergy, atopic eczema, chronic dermatitis, severe psoriasis, multiple sclerosis, severe asthma, lupus or related disorders
• Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions
• Smoking (regular or irregular) \> 5 cigarettes (or equivalent) per day
• Excessive alcohol drinking (more than approximately 20 g alcohol per day), unable to refrain from alcohol drinking from 48 hours prior to dosing until the last pharmacokinetic blood sample has been withdrawn

Sponsors & Collaborators

• Phenex Pharmaceuticals AG: lead

Study Sites (1)

FOCUS Clinical Drug Development GmbH

Neuss, Germany

Location

MeSH Terms

Interventions

PX-102

Study Officials

• Claus Kremoser, Dr.

  Phenex Pharmaceuticals AG

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: December 2, 2013
• Study Start: February 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 4, 2014

Record last verified: 2014-11

Locations

DE (1)