Safety Study of Px-104 in Patients with liver disease

• Conditions: on-alcoholic fatty liver disease (NAFLD); MedDRA version: 16.1Level: PTClassification code 10024670Term: Liver disorderSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2013-002984-24-AT
• Lead Sponsor: Phenex Pharmaceuticals AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-31
• Last Update Posted: 16 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Male or females
•Age 18-70 years
•Diagnosis of NAFLD as defined as (all of the following 5 points must apply):
1.NAFLD on liver biopsy within 2 years prior to study participation OR liver steatosis on any imaging (ultrasound, MRI, CT)
2.Disturbed metabolic homeostasis based on impaired HOMA-IR > 1
3.ALT within or above the upper tertial of the ULN (ALT < 45 for males, < 35 for females U/l) and/or GGT above ULN (GGT < 55 for males, < 38 for females U/l)
4.Steatosis > 15% at CAP Fibroscan at screening
5.Steatosis > 10% equivalent to histology at 1H-MRS at baseline
•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.
•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. Effective methods of contraception are considered to be:
?Condom (male or female)
?Diaphragm, with spermicide
?Hormonal (e.g. contraceptive pill, patch, intramuscular implant or injection)
?Intrauterine device (IUD)
?Vasectomy (partner)
•Must be willing and able to give written informed consent and agree to comply with the study protocol.
•Sinus rhythm in 12-lead ECG

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

• Evidence of excessive alcohol, drug or substance abuse
•History or other evidence of a medical condition associated with chronic liver disease other than NAFLD
•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
I. History of any structural cardiac disease requiring treatment:
•Any signs or symptoms of heart failure (NYHA II-IV)
•History of ventricular tachyarrhythmia requiring ongoing treatment
•History of bradyarrhythmia requiring Pacemaker treatment
•Relevant coronary artery disease
oHistory of myocardial infarction
ostable or unstable angina
II. Any clinically relevant findings in ECG at screening:
•Conduction abnormalities
oAV-Block 2nd (Type II) or 3rd degree
oPauses > 3seconds
•Ventricular arrhythmia
oMonomorphic or polymorphic ventricular ectopic beats = 30 beats/ hours calculated as mean over the continuous ECG recording period.
oNon-sustained ventricular tachycardia (three or more consecutive ventricular beats at a rate of greater than 100 beats/min)
•Atrial arrhythmia
oAtrial ectopic beats = 30 beats/ hours calculated as mean over the continuous ECG recording period.
oRe-entrant supraventricular tachycardia
•Any type of tachycardia at rest (frequency >120/min at rest) in 12-lead ECG
•Sinus bradycardia <40 bpm as minimum recorded heart rate in 12-lead ECG or bradycardia <35 bpm in 24h Holter ECG
•Prolongation of QTc interval (QTc interval > 440 ms for male subjects or > 480 ms for female subjects) of >10% over 24 hours using the Fridericia method for QTc analysis.
IIII. 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.
IV. History of cerebrovascular disease:
•History of any stroke or transient ischemic attack
•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
•Known sensibility to any ingredients contained in the IMP
•All conditions that do not allow 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.
•Woman with childbearing potential unless using adequate contraception; females who are pregnant or breast feeding.
•History of severe allergic or immunologically mediated disease [(e.g., vasculitis, cryoglobulinemia, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis (defined as affecting > 10% of the body, where the palm of one hand equals 1%, or if the hands and feet are affected), rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management, etc.]
•Evidence of an active or suspected cancer, or a history of malignancy within the last 2

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified