Healthy
Conditions
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.
Detailed 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.
Interventions
DRUGPx-102
Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg
DRUGPlacebo
Drinking solution
Sponsors
Phenex Pharmaceuticals AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of Px-102 | 7 days | Adverse event monitoring, laboratory values, cardiovascular monitoring. Comparison active vs. placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Plasma, urine and fecal concentrations (ng/mL) of Px-102 and metabolites measured by LC-MS/MS. AUC, Cmax and other pk parameters. Comparison of the pk data on day 7 vs. day 1 |
| 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 | Markers for FXR activation (e.G. FGF19 (pg/mL) measurement by ELISA). Comparison active vs. placebo |
Countries
Germany
Outcome results
None listed