Trial of MitoQ for Raised Liver Enzymes Due to Hepatitis C

NCT00433108 | Completed Phase 2

• 1 other identifier: MTQ-HC-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 2, randomized, double-blind, parallel design trial of two doses of mitoquinone mesylate (MitoQ) and of placebo in patients with chronic Hepatitis C. MitoQ is a mitochondria-targeted antioxidant that rapidly permeates the lipid bilayer and accumulates within mitochondria in organs such as liver, brain, heart, skeletal muscle. There is strong evidence for increased oxidative stress and mitochondrial damage leading to apoptosis via caspase activation. Several studies have shown that MitoQ protects cells from apoptosis by acting as a caspase inhibitor and may be effective in reducing cell damage in liver disease. It is hypothesised that administration of MitoQ will lower raised ALT seen in patients with chronic Hepatitis C compared with placebo. Approximately 36 patients who have been unresponsive or not suitable for interferon-based therapy will be enrolled at one centre. Treatment duration will be 28 days with 28 days post-treatment follow-up.

Conditions

Chronic Hepatitis C

Keywords

Hepatitis C; antioxidant; liver enzymes; ALT

Outcome Measures

Primary Outcomes (1)

• Change in serum ALT concentration at Day 28 compared with baseline

Secondary Outcomes (2)

• Efficacy: Change in AST at Day 28 compared with baseline, change in HCV RNA viral load, plasma Mitoquinone concentration for population pharmacokinetics

• Safety: Adverse events, vital signs, ECG, lab tests (biochemistry, hematology, urinalysis)

Interventions

Mitoquinone mesylate (MitoQ) DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to adhere to study requirements as evidenced by providing written informed consent before initiation of any study-related procedures
• Aged between 18-65 years
• Documented history of chronic HCV infection (for at least 6 months prior to study entry) as diagnosed by either:
• Anti-HCV positive or
• HCV RNA viral load positive by PCR
• Be a non-responder to or unsuitable for interferon based therapy.
• Have liver inflammation, as defined by either AST and/or ALT levels 2-10 x ULN on at least 1 previous occasion within the past 6 months and at Pre-treatment visit
• alpha-fetoprotein (AFP) less than/equal to 50µg/L
• Hemoglobin ≥100g/L, platelet count ≥75x109/L, and white blood cell count ≥1.5x109/L
• Males, or females who are not of child-bearing potential or who are taking adequate contraceptive measures. Female patients must be postmenopausal for at least 2 years prior to the study, surgically sterile, or using effective contraception for at least 2 months prior to starting study drug and until 28 days following the last dose of study drug. Acceptable methods of birth control include hormonal contraceptives, or double-barrier methods.Negative serum pregnancy test must be documented at the Pre-treatment visit (i.e. within 14 days of starting study drug)
• Liver biopsy within past 3 years showing stage 2 fibrosis only (i.e. excludes cirrhosis and cancer); or within past 6 years showing stage 0 or 1 (no or minimal scarring).

You may not qualify if:

• Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques)
• Presence of human immunodeficiency virus (HIV)
• Co-infection with hepatitis B virus (HBV)
• Last baseline AST and ALT level prior to Day 1 of \<2.0xULN
• Renal impairment (creatinine\>1.5 x ULN) or hepatorenal syndrome
• Chronic pancreatitis
• Hospitalization for liver disease within 60 days of the Pre-treatment visit
• Liver transplant recipients
• Use of drug therapy for Hepatitis C, including the use of:
• drugs with presumed anti-Hepatitis C activity in the past 3 months
• corticosteroids in the past 30 days
• drugs with medium to high risk of hepatotoxicity (including alpha methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) in the past 30 days
• Any patient who admits to using or has a positive screening test for: amphetamines, barbiturates, pethidine, benzodiazepine, cocaine, methadone, opiates, phencyclidine or propoxyphene (unless medically prescribed and in stable doses for at least 30 days)
• Alcohol consumption \>5 units per week
• Any patient who has received any investigational drug or device within 30 days of dosing, or who is scheduled to receive another investigational drug or device during the course of this trial

Sponsors & Collaborators

• Antipodean Pharmaceuticals, Inc.: lead

Study Sites (2)

New Zealand Liver Unit, Auckland City Hospital

Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

Related Publications (1)

• Gane EJ, Weilert F, Orr DW, Keogh GF, Gibson M, Lockhart MM, Frampton CM, Taylor KM, Smith RA, Murphy MP. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010 Aug;30(7):1019-26. doi: 10.1111/j.1478-3231.2010.02250.x. Epub 2010 May 18.

  PMID: 20492507 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

mitoquinone

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Edward J Gane, MBChB

  Liver Transplant Unit, Auckland City Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 7, 2007
• First Posted: February 9, 2007
• Study Start: March 1, 2007
• Study Completion: November 1, 2007
• Last Updated: August 14, 2008

Record last verified: 2008-08

Locations

NZ (2)