Phase I, Dose-Escalation Clinical Trial to Evaluate the Safety and Tolerability of Pentoxifylline PKB171 Gel in Single-Dose Intravaginal Administration, Followed by an Extension Study With Multiple-Dose Administration in Healthy Volunteers

Phase I, randomised, double-blind, placebo-controlled, dose-escalation study to determine the MTD of PKB171 after single-dose intravaginal administration, followed by a double-blind extension study with multiple-dose vaginal administration (two consecutive days) of PKB171at the MTD in healthy volunteers.

Part A. Dose-Escalation:

A single dose of PKB171 vaginal gel (5 g) was intravaginally administered to healthy volunteers. Three strengths of PKB171 gel were tested: 2% (100 mg pentoxifyline), 3% (150 mg pentoxifyline) and 4% (200 mg pentoxifyline).

Three cohorts of 8 healthy female volunteers participated. Intrapatient dose escalation was not permitted. For each dose level, subjects were randomly allocated to receive either the study drug or the placebo (3:1) between day 7 and 21 of their menstrual cycle. In the first cohort (cohort A), a first volunteer received the study drug; after 24 hours of safety assessment, the rest of the volunteers of that cohort received the study drug (5 volunteers) or placebo (2 volunteers).

Safety and tolerability of each strength level and dose-escalation decisions were made based on the occurrence of drug-related adverse events (AEs). The maximum tolerated dose (MTD) in terms of local tolerability was defined as the highest dose at which no more than 1 of 6 patients experienced a moderate or severe drug-related adverse events following PKB171 gel administration. Dose escalation proceeded until the highest strength of PKB171 vaginal gel (4%) or matching placebo.