Clinical Trial Result Information
- Protocol number:
- Title of Study:
- Prospective, randomized, single-blind, cross-over, comparative study for establishing comparative bioavailability of Copegus vs Vilona® in healthy volunteers
- Hoffmann-La Roche
- Company division:
- Product name:
- Generic name:
- ribavirin [Copegus]
- Therapeutic area:
- Healthy Volunteer
- Clinical study summary:
This prospective, randomized, single-blind, cross-over study was designed to compare the bioavailability of Copegus (ribavirin) administered as tablets and ribavirin administered as capsules in healthy volunteers. Volunteers were randomized to one of two sequences, Sequence 1: reference drug and then test drug; Sequence 2: test drug and then reference drug.
- Study center(s):
Single center in Mexico
- Phase of development:
The objective was to compare the bioavailability of two pharmaceutical formulations of ribavirin
After screening and signing the informed consent form, eligible healthy volunteers were enrolled in the study. On Day 1, volunteers received the ribavirin formulation they were randomized too. Blood samples were taken on Days 1 to 5. After a washout period of 14 days, volunteers received the other ribavirin formulation. Safety was monitored throughout the study.
- Number of patients (planned/analyzed):
- 40 volunteers planned and enrolled
- Diagnosis and main criteria for inclusion:
Adult healthy volunteers, 18 to 55 years of age; Clinically healthy as confirmed by medical history, physical examination, electrocardiogram, thorax teleradiography and routine clinical laboratory measurements; Body mass index between 18 and 28 kg/m2; Negative testing for drugs of abuse
- Test product, dose and mode of administration or test procedure:
ribavirin (Copegus) 400 mg tablets (single oral dose)
- Duration of treatment:
- 1 day for each sequence
- Reference therapy, dose and mode of administration or reference procedure:
ribavirin (Vilona®) 400 mg capsule (single oral dose)
- Criteria for evaluation (efficacy, safety):
Cmax, Tmax, AUC0-t, AUC0-inf, T½, MRT0-t, MRT0-inf
Adverse events, physical examination, medical history, vital signs, laboratory parameters
- Statistical methods:
For the statistical analysis, pharmacokinetic parameters were analyzed by analysis of variance (ANOVA) using a linear statistical model. To estimate the bioequivalence between the test drug and the reference drug, the pharmacokinetic parameters of Cmax, AUC0-t and AUC0-inf were subjected to the double one-sided t test; to the Classical confidence intervals and Westlake, as well as the Anderson-Hauck test. Each parameter was determined at a value of α=0.05 and a value of β=0.20 to detect the difference between the test drug and the reference drug. Safety parameters were analyzed descriptively.
- Summary (efficacy, safety, other results):
40 male healthy volunteers were enrolled in the study. The mean age was 21.4 years (SD 3.46; CI 16.15). The mean weight was 67.89 kg (SD 9.46; CI 13.94). The mean height was 167 cm (SD 0.084, CI 5.01). The mean body mass index was 24.3 (SD 2.64, CI 10.88). The mean years of schooling was 14 (SD 2.22; CI 15.85).
The following pharmacokinetic parameters were obtained for the test drug Copegus and the reference drug Vilona®:
Tmax = Time in which the Cmax is reached
λz = Slope of the lineal portion of the elimination phase value
T½ = Half-life time of λz
MRT = Mean residence time
SD = Standard Deviation
ANOVA was performed with the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-Inf. For Cmax, there was no significant effect for the sequence (p=0.8342; alpha=0.05), but for the period (p=0.0066; alpha=0.05). However, since the study used a balanced design, the difference found in the period was not considered as relevant.
For AUC0-t, and AUC0-Inf, there were no significant effects for the sequence (p=0.9322; alpha=0.05 and p=0.7806; alpha=0.05, respectively), or the period sequence (p=0.9307; alpha=0.05 and p=0.1205; alpha=0.05, respectively).
Confidence intervals were between 80 to 125 and the Unilateral test, double-one-sided test and the Hauck-Anderson test showed a value of less than 0.05, all of the tests had a power equal or greater than 0.8 establishing the bioequivalence of the two ribavirin formulations.
There were 7 adverse events (AEs) in 7 patients during the study. All AEs were not considered to be related to the study drug. All patients had recovered at the end of the study.
No serious adverse events were reported.
The results of the bioequivalence study confirmed that the bioavailability and the pharmacokinetics of Copegus as tablet formulation and Vilona® as capsule formulation are comparable.
- Date of report:
About This Database
This database is populated with information on the results of Roche-sponsored clinical trials.