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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02118012
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : February 15, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Brief Summary:


- 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.


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


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


  • 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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: Chlorcyclizine HCL plus Ribavirin Drug: Chlorcyclizine HCL Only Phase 1

Detailed Description:
Up to 50 patients with chronic hepatitis C, who are treatment na(SqrRoot) ve or relapsers to any interferon/ribavirin regimen will be enrolled into this pilot study evaluating chlorcyclizine HCl with or without ribavirin (RBV) as antiviral therapy. Adult patients (greater than or equal to18 years of age) with evidence of active chronic hepatitis C infection (all genotypes) with detectable HCV RNA in serum >10,000 IU/mL without contraindications to chlorcyclizine HCl or ribavirin or evidence/history of hepatic decompensation will be enrolled. Patients will be monitored for at least two months with regular testing for ALT and HCV RNA quantitative levels before treatment and will undergo admission to start therapy, which includes a thorough medical evaluation and timed blood sampling. Patients will be randomized to one of two treatment groups; one with chlorcyclizine HCl (75 mg twice daily) and the other with RBV+ chlorcyclizine HCl (75 mg twice daily). For all genotypes, RBV will be dosed based on weight (1000 mg daily <75 kg and 1200 mg daily greater than or equal to 75 kg). At each clinic visit, patients will be questioned about side effects and symptoms, undergo a focused physical examination, and have blood taken for complete blood counts, HCV RNA, PT/INR and routine liver tests (ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At the end of 28 days of treatment, patients will undergo a repeat thorough medical evaluation inclusive of a complete physical exam, symptom scale evaluation, complete blood counts, routine liver tests, and HCV serology panels. The primary endpoint of therapy will be a decline in quantitative HCV RNA viral levels after 28 days of treatment as compared to baseline viral titers and between groups. Several secondary endpoints will be measured, including side effects of therapy, ALT levels, quantification of chlorcyclizine HCl and its metabolites in serum, and quality of life. Therapy will be stopped for intolerance to RBV and/or chlorcyclizine HCl (which will be carefully defined).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl Alone or in Combination With Ribavirin in Patients With Chronic Hepatitis C
Study Start Date : March 20, 2014
Actual Primary Completion Date : March 20, 2014
Actual Study Completion Date : September 20, 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Chlorcyclizine and RBV
Chlorcyclizine HCl and Ribavirin
Drug: Chlorcyclizine HCL plus Ribavirin
RBV+ chlorcyclizine HCl (75 mg twice daily)

Active Comparator: Chlorcyclizine HCl only
chlorcyclizine HCl (75 mg twice daily)
Drug: Chlorcyclizine HCL Only
chlorcyclizine HCl (75 mg twice daily)

Primary Outcome Measures :
  1. Decline in serum HCV RNA viral titer during therapy as compared to baseline measured by PCR. The ability to tolerate the drug at the prescribed dose for the duration of therapy. [ Time Frame: Day 28 of therapy ]

Secondary Outcome Measures :
  1. 1. A significant change in alanine aminotransferase (ALT) levels compared to baseline.2. Quantification of chlorcyclizine HCL and its metabolites in serum during therapy.3. Changes in symptom scale measurements during and after therapy. [ Time Frame: Day 28 of therapy ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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;


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02118012

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Christopher Koh, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT02118012     History of Changes
Other Study ID Numbers: 140084
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: September 6, 2018

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Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):
Chlorcyclizine HCL
Direct Acting Antivirals
Chronic Hepatitis C

Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents