Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl Alone or in Combination With Ribavirin in Patients With Chronic Hepatitis C

• Status: Completed
• Trial end date: 0000-00-00
• Target enrollment: 27
• Participant gender: Both

Summary

Background:

• Hepatitis C is a liver disease caused by the hepatitis C virus. It is the most common cause of serious liver disease in the United States. Many people have few if any symptoms. It can lead to cirrhosis, which can cause liver failure and cancer. Researchers want to study how a medicine called chlorcyclizine works in patients with hepatitis C. They want to see if it can be used to treat hepatitis C alone or when used with the standard hepatitis C treatment drug ribavirin.

Objectives:

• To see if chlorcyclizine can be used to treat hepatitis C alone or in combination with the drug ribavirin.

Eligibility:

• Adults with chronic hepatitis C who either have never been treated for it or have relapsed after prior treatment.

Design:

• Participants will be screened with medical history, physical exam, blood and urine tests, and a questionnaire. They will also have an ultrasound of their abdomen and electrocardiogram. Some of these tests will be repeated throughout the study.

• Participants will spend 3 days as an inpatient to be monitored while starting study drug. They will be assigned randomly to a group and will begin taking the study drug. Blood will be taken frequently.

• Group I will take the study drug twice a day for 28 days.

• Group II will take the study drug twice a day and ribavirin twice a day for 28 days.

• Participants will visit the clinic every 7 days for 28 days.

• After participants stop taking the study drug, they will have 5 follow-up visits over 3 months.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Antiviral Agents; Ribavirin
• Last Updated: 2016-09-21

Criteria

• INCLUSION CRITERIA:

• Adults, ages 18 and above;

• Chronic hepatitis C (HCV RNA in serum for more than 6 months);

• HCV RNA in serum at or above 10,000 IU/mL;

• Treatment naive patients defined as individuals whom have never undergone any form of interferon and ribavirin therapy for chronic HCV infection or relapsers defined as reappearance of HCV RNA in serum after treatment (with any form of interferon and ribavirin therapy) was discontinued and an end-of-treatment response was achieved;

• No major contraindications to agents being used (chlorcyclizine HCl and ribavirin);

• Females of childbearing potential must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug;

• Women of childbearing potential and men, participants and partners, must use highly effective methods of birth control to minimize the risk of pregnancy and must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of ribavirin. Two forms of birth control are required from the time of screening throughout the duration of the on-treatment study period and for at least 24 weeks after the last dose of ribavirin. Examples of effective birth control include: condom with spermicide; diaphragm with spermicide; cervical cap with spermicide; female condom; intrauterine devices (IUDs); vasectomy in men;

EXCLUSION CRITERIA:

• Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair;

• Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment;

• Documented or suspected HCC, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed);

• Evidence of decompensated liver disease including, but not limited to, bilirubin >4 mg/dL, albumin <3.0 gm/dL, prothrombin time >2 sec prolonged or a history or presence of ascites, bleeding varices, or hepatic encephalopathy. Patients with ALT levels >500 U/L will not be enrolled but may be followed until three determinations are below this level;

• Evidence of a medical condition contributing to chronic liver disease other than chronic HCV infection (such as, but not limited to: acute hepatitis C infection, hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures);

• History of chronic hepatitis B virus (HBV) as documented by HBV serologies (eg, HBsAg-seropositive). Subjects with resolved HBV infection may participate (eg, HBsAb-seropositive with concurrent HBsAg-seronegative);

• Any prior exposure to direct-acting antiviral therapies for chronic HCV infection;

• History of HIV infection;

• History of hemoglobinopathies (eg. thalassemia major or sickle cell anemia), diagnoses associated with an increased baseline risk for anemia (eg, spherocytosis), hemolytic anemia, or diseases in which anemia would be medically problematic, or hemophilia;

• Confirmed, uncontrolled hypertension (any screening systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg should be excluded unless discussed with the central medical monitor);

• Any other medical and/or social reason, including active substance abuse as defined by DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse, which in the opinion of the investigator would make the candidate inappropriate for participation in this study;

• Significant systemic or major illnesses other than liver disease, including, but not limited to, clinically significant emphysema or chronic bronchitis, symptomatic benign prostatic hypertrophy, glaucoma, gastrointestinal motility related illnesses, congestive heart failure, renal failure (eGFR <50 mL/min), and active coronary artery disease;

• Significant prior history suggestive of cardiovascular instability, including but not limited to evidence of significant myocardial ischemia, unstable re-entry phenomena, other significant dysarrhythmias and/or uncontrolled hypertension;

• Inability to tolerate oral medication;

• For relapsers: exposure to interferon based therapy with ribavirin within 12 weeks prior to screening;

• Allergy or hypersensitivity to chlorcyclizine HCl or ribavirin;

• Any known contraindication to ribavirin, not otherwise specified;

• Inability to refrain from operating heavy machinery while on therapy;

• Breastfeeding women;

• Inability to understand or sign informed consent;

• Active use of chlorcyclizine HCl or another piperazine class antihistamine within 6 months of enrollment;

• Inability to abstain from piperazine class antihistamines during enrollment in the clinical trial period.