NCT07017114

Pentoxifylline PKB171 Gel in Healthy Females Volunteers

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Prokrea BCN, S.L. · Industry
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

A Phase I, Randomised, Double-Blind, Placebo-Controlled, 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. The primary ojective was to determine the maximum tolerated dose (MTD) in terms of local tolerability of PKB171 after single-dose intravaginal administration in healthy female volunteers; the secondary objectives evaluated the safety and tolerability of PKB171 after single-dose intravaginal administration and the pharmacokinetic (PK) profile of PKB171 after single-dose intravaginal administration. The extension substudy evaluated the safety and tolerability of PKB171 after multiple-dose intravaginal administration at the MTD in healthy volunteers.

Detailed description

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. To obtain a full PK profile of PKB171 at each dose, blood samples (10 ml) were collected at baseline (pre-treatment), 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 h, 2 h, 4 h, 8 h and 24 hours post-administration (10 blood draws in total) to analyse the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, T1/2, Vd, Clp) of PKB171 and its metabolite 5-OH-pentoxifylline. Part B. Multiple-dose extension substudy: After completing the dose-escalation phase, an extension substudy was planned in order to assess the tolerability and PK of PKB171 after multiple-dose administration (two consecutive days) using the MTD in healthy female volunteers. A subgroup of 6 patients that have participated in the first part of the study were invited to participate in the randomised, parallel-group, placebo-controlled extension study. Patients were randomly allocated to receive either the study drug or the placebo (2:1) between day 7 and 21 of their menstrual cycle. The MTD of PKB171 gel or matching placebo (5 g) were administered intravaginally in two consecutive days.

Conditions

• Safety
• Pharmacokinetics
• Maximum Tolerated Dose

Interventions

Type	Name	Description
DRUG	Gel PKB171	Subjects received a single dose of pentoxifylline PKB171 gel or placebo, in a one-dose form with an applicator device that allowed for vaginal administration following the randomisation list: * First dose level: 2% (100 mg) * Second dose level: 3% (150 mg) * Third dose level: 4% (200 mg) The treatment was provided by a member of the investigator's staff and self-administered by volunteers under clinical supervision. The dose-escalation process enabled to determine MTD or the highest dose that was safe to administer in later studies was determined. The results of this study helped to define the recommended doses to be used in the multiple-dose extension.
DRUG	Gel PKB171 placebo	PKB vaginal gel at the MTD or placebo once every 24 hours for two consecutive days

Timeline

• Start date: 2016-01-27
• Primary completion: 2016-04-26
• Completion: 2016-09-21
• First posted: 2025-06-12
• Last updated: 2025-06-12