Clinical trial NCT01998659: Single Ascending Oral Dose Phase I Study With Px-102
Official title: A Double-blind, Randomized, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Pharmacokinetics of Increasing Single Oral Doses of Px-102 to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Phenex Pharmaceuticals AG
Sponsor class: INDUSTRY
First posted: 2013-12-02
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of the FXR agonist Px-102 in healthy subjects after single oral dosing.

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

Eligibility criteria: Inclusion Criteria:

* Healthy male subject of caucasian origin 18 to 45 years of age
* 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 with absolute weight in between 70-120 kg.
* Serum triglyceride, 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.
* 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

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/1,73m2 (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
* 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.
* 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 h 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
* All subjects (including male subjects with partners of childbearing potential) who do not 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 contraceptives in combination with a barrier method, some intrauterine contraceptive devices or sexual abstinence
* Any condition or previous disease leading to puritus or itching of the skin.

Primary outcomes:
measure: Safety and tolerability of Px-102
timeFrame: 24h
Secondary outcomes:
measure: Pharmacokinetics of Px-102 and metabolites
timeFrame: pre-dose (0 hours), 15 min, 30 min, 1, 1.5, 2, 4, 6, 8, 12, 24 hours after dosing
measure: Pharmacodynamics
timeFrame: pre-dose (0 hours) and 1, 2, 4, 8, 12, and 24 hours
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: FOCUS Clinical Drug Development GmbH
Study officials:
affiliation: Phenex Pharmaceuticals AG
name: Claus Kremoser, Dr.
role: STUDY_CHAIR
References: