OBJECTIVE: To assess the relative bioavailability of diclofenac sodium hydroxypropyl β-cyclodextrin (HPβCD) administered via the subcutaneous (s.c.) and intramuscular (i.m.) route versus Voltaren® i.m. and to evaluate the dose linearity and pharmacokinetics of the s.c. formulation at three dose levels. Safety and local tolerability were also assessed. MATERIALS AND METHODS: One single-dose, randomized, three-way, crossover relative bioavailability study and one linearity single escalating dose, randomized, three-way cross-over pharmacokinetic study were conducted at two different clinical sites. A total of 42 healthy male and female subjects participated in both studies. Subjects received 75 mg/ml diclofenac sodium HPβCD (i.m. and s.c.) and Voltaren® 75 mg/3 ml (i.m.) in Study 1 and 25, 50, or 75 mg/ml diclofenac sodium HPβCD (s.c.) in Study 2. RESULTS: Study 1 demonstrated bioequivalence of the s.c. test formulation with Voltaren® i.m. with respect to Cmax and AUC. Bioequivalence of the test i.m. with Voltaren® i.m. was also demonstrated (except the upper limit of the 90% confidence interval (CI) for Cmax which marginally exceeded the 80 - 125% range (125.78%)). Study 2 demonstrated that after s.c. administration of the test formulation, both Cmax and AUC are linearly related to the tested diclofenac doses. All tested doses were safe and locally well-tolerated with no serious adverse events reported. CONCLUSION: Bioequivalence of diclofenac HPβCD 75 mg/ml after s.c. and i.m. administration with Voltaren® i.m. was demonstrated, except for the marginal deviation in Cmax when comparing the i.m. test and Voltaren®. Linearity was also demonstrated for the three doses intended for marketing.
RCT Entities:
OBJECTIVE: To assess the relative bioavailability of diclofenac sodium hydroxypropyl β-cyclodextrin (HPβCD) administered via the subcutaneous (s.c.) and intramuscular (i.m.) route versus Voltaren® i.m. and to evaluate the dose linearity and pharmacokinetics of the s.c. formulation at three dose levels. Safety and local tolerability were also assessed. MATERIALS AND METHODS: One single-dose, randomized, three-way, crossover relative bioavailability study and one linearity single escalating dose, randomized, three-way cross-over pharmacokinetic study were conducted at two different clinical sites. A total of 42 healthy male and female subjects participated in both studies. Subjects received 75 mg/ml diclofenac sodium HPβCD (i.m. and s.c.) and Voltaren® 75 mg/3 ml (i.m.) in Study 1 and 25, 50, or 75 mg/ml diclofenac sodium HPβCD (s.c.) in Study 2. RESULTS: Study 1 demonstrated bioequivalence of the s.c. test formulation with Voltaren® i.m. with respect to Cmax and AUC. Bioequivalence of the test i.m. with Voltaren® i.m. was also demonstrated (except the upper limit of the 90% confidence interval (CI) for Cmax which marginally exceeded the 80 - 125% range (125.78%)). Study 2 demonstrated that after s.c. administration of the test formulation, both Cmax and AUC are linearly related to the tested diclofenac doses. All tested doses were safe and locally well-tolerated with no serious adverse events reported. CONCLUSION: Bioequivalence of diclofenac HPβCD 75 mg/ml after s.c. and i.m. administration with Voltaren® i.m. was demonstrated, except for the marginal deviation in Cmax when comparing the i.m. test and Voltaren®. Linearity was also demonstrated for the three doses intended for marketing.