A Phase 1, Open-Label, Four-Period, Two-Sequence, Two-Treatment, Single Dose, Randomized, Crossover Bioequivalence Study of a Test Tablet Formulation of Ravidasvir with the Reference Tablet Formulation of Ravidasvir in Healthy Adult Volunteers Under Fasting Conditions
Drug for Neglected Diseases initiative
36 participants
Feb 14, 2020
Interventional
Conditions
Summary
Ravidasvir, is being developed for the treatment of Hepatitis C, a liver disease caused by a virus (HCV). Ravidasvir is a NS5A inhibitor, which exhibits potent inhibition of HCV replication in HCV replicon assays. In an ongoing phase II/III study, it was hypothesized that sofosbuvir plus ravidasvir constitutes a pan-genotypic, potent and safe regimen which can be used in decentralized public health settings under the supervision of appropriately trained health care professionals. Such a combination will not require intensive pre-treatment evaluation or monitoring and can thus be scaled up together with active identification and linkage to care of HCV infected persons. 301 patients were included in the study and preliminary data are very promising. During the course of development, a new batch of ravidasvir tablets has been prepared by the proposed commercial manufacturer (Doppel Farmaceutici, Italy) with an Active Pharmaceutical Ingredient (API) manufactured by Pharco B International (Egypt). Tablets manufactured from the Pharco B international API are intended to be used in subsequent clinical trials and be registered as the commercial product. We are doing this assay to assess if ravidasvir 200 mg tablets supplied by Doppel Farmaceutici from CAD Middle East Pharmaceutical Industries LLC (Saudi Arabia) API and tablets from Doppel Farmaceutici from the Pharco B international API are bioequivalent. The study will be done at a single site: Clinical Research Ward at Ampang Hospital.
Eligibility
Inclusion Criteria14
- • Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
- • Must be between 18 and 55 years of age, inclusive, at the date of ICF signature
- • Must be a non-smoker or an ex-smoker for more than 90 days. The use of nicotine or nicotine-containing products or electronic cigarettes must be discontinued 90 days prior to the first admission day of the study.
- • Must have a calculated body mass index (BMI) of 18.0 to 29.9 kg/m2.
- • Must be HIV-1 antibody negative.
- • Must be hepatitis B (HBV) surface antigen negative.
- • Must be hepatitis C (HCV) antibody negative.
- • Females must have a negative serum pregnancy test at Screening and on Day 0.
- • Females of childbearing potential must agree to utilize highly effective contraception methods (with the exception of hormonal contraceptive) from 3 weeks prior to baseline (Day 0) throughout the duration of study treatment and for 30 days following the last dose of study drug.
- • Men who participate in this study must not father a child and must agree to use contraceptive protection in the form of a double barrier method (condom or diaphragm) from the moment they sign the ICF until the Post-Study Safety Assessment.
- • Healthy volunteers must, in the opinion of the Investigator, be in good health based upon medical history, physical examination (including vital signs), and screening laboratory evaluations (haematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined and documented by the Investigator to have no clinical significance.
- • Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered not clinically significant by the Investigator. QTcF measure should be less than or equal to 450 msec (male) or than or equal to 470 msec (female).
- • Must have negative urine screen for drugs of abuse (including but not limited to ketamine, amphetamines, tetrahydrocannabinol, morphine, methamphetamine, and benzodiazepines)
- • Must be willing and able to comply with all study requirements.
Exclusion Criteria15
- • Healthy volunteers with any hematologic or urinary analyte that is outside the normal limits of the study laboratory and have been determined by the Investigator to have clinical significance at Screening will be excluded
- • Pregnant or lactating female healthy volunteers.
- • Female healthy volunteers who utilize hormonal contraceptive as one of their birth control methods.
- • Have any serious past or active medical condition or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematologic, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central or peripheral nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), surgery (e.g stomach bypass) or immunodeficiency disorders, active infection, or malignancy that is clinically significant or requiring treatment.
- • Have participated in an investigational trial involving administration of any investigational compound within 90 days prior to the study dosing or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial).
- • Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
- Regular alcohol consumption in males greater than 21 units per week and females greater than 14 units per week (1 unit equal ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units equal 125 mL glass of wine, depending on type). As confirmed by a positive alcohol breath test either at screening or at admission day.
- • Have donated or lost blood (greater than or equal to 450ml) within three months of study dosing.
- • Have donated plasma within 7 days of study dosing.
- • Have difficulty in swallowing solids like tablets.
- • Have taken any prescription medications or over-the-counter medications including herbal products within 1 week of commencing study drug dosing with the exception of vitamins (without herbal compounds) and/or paracetamol and/or ibuprofen.
- • Have a history of significant drug allergy.
- • Smokers as confirmed by a breath carbon monoxide (Smokerlyzer) reading of greater than 10 ppm at screening or at admission day, and users of electronic cigarette.
- • Unable and/or unwilling to comply with study requirements.
- • Believed by the study Investigator to be inappropriate for study participation for any reason
Interventions
In the First group, the Comparator Treatment Ravidasvir Reference product will be administered as a single dose of 200 mg [1 x 200 mg] tablet on Day 1 and Day 15 with approximately 240 mL of ambient temperature water under fasted conditions. On day 8 and Day 22, the First group will receive a single dose of 200 mg [1 x 200 mg] tablet of the Interventional Treatment Ravidasvir Test product with approximately 240mL of ambient temperature water under fasted conditions. Each dose of RDV (first dose on Day 1, second dose on Day 8, third dose on Day 15 and last done on Day 22) will be separated by a washout period of at least 7 days. In the Second group, the Interventional Treatment Ravidasvir Test product will be administered as a single dose of 200 mg [1 x 200 mg] tablet on Day 1 and Day 15 with approximately 240 mL of ambient temperature water under fasted conditions. On day 8 and Day 22, the Second group will receive a single dose of 200 mg [1 x 200 mg] tablet of the Comparator Treatment Ravidasvir Reference product with approximately 240mL of ambient temperature water under fasted conditions. Each dose of RDV (first dose on Day 1, second dose on Day 8, third dose on Day 15 and last done on Day 22) will be separated by a washout period of at least 7 days. To ensure that subjects will be under fasted conditions, they will be admitted the day before the dosing day at the admission unit. They will be fasting since 10:00 pm until until 4 hours after dosing (total 14 hours). Water only will be allowed except during 1 hour before and 1 hour after dosing. Patients will stay at the admission unit during 3 days
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ACTRN12620000037909