Multiple Ascending Oral Dose Phase I Study With Px-102

Phenex Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Placebo

Drug: Px-102

Study type

Interventional

Funder types

Industry

Identifiers

NCT01998672

PHS-Px-102-I-02

Details and patient eligibility

About

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.

Full description

The study is a single-centre, double-blind, randomized, placebo-controlled, parallel group phase I study with healthy male subjects receiving ascending multiple oral oral doses of Px-102 to assess the safety and tolerability, pharmacokinetics and pharmacodynamics.

Enrollment

42 patients

Sex

Male

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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
Positive test for drugs or alcohol at screening or prior to the dosing session
History of alcoholism or drug/chemical/substance abuse within past 2 years
Investigator deems the subject unable or unwilling to comply fully with the study protocol
Has received clinical study medication within the last 30 days prior to this study
Donation or loss of 400 ml or more of blood within eight (8) weeks prior to dosing
Allergic to any of the active or inactive ingredients in the study medication
Any other reason which the Investigator considers unsuitable for the subject to participate
Any condition or previous disease leading to pruritus or itching of the skin.