Pentoxifylline PKB171 Gel in Healthy Females Volunteers

NCT07017114 | Completed Phase 1

• 2 other identifiers: PKB171-012015-004611-21
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Safety; Pharmacokinetics; Maximum Tolerated Dose

Keywords

Pharmacokinetics; Maximum tolerated dose (MTD); Local tolerability; pentoxifyline PKB171 Gel

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of PKB171

  To determine the maximum tolerated dose (MTD) of PKB171 according to the dose at which a related adverse event occurs in one or more subjects.

  3 weeks

Secondary Outcomes (11)

• Adverse events

  3 weeks

• Local reactions of PKB171

  3 weeks

• Visual Analogue Scale

  3 weeks

• Pregnancy

  3 weeks

• Peak Plasma Concentration (Cmax)

  3 weeks

Study Arms (4)

PKB vaginal gel, at 100 mg pentoxifyline (2% gel).

EXPERIMENTAL

Regarding the dosing schedule, on day 1 of the study (Visit 1) a single dose of investigational drug (of each concentration) or placebo, were administered by intravaginal via using an applicator device (syringe).

Drug: Gel PKB171; Drug: Gel PKB171 placebo

PKB vaginal gel, at 150 mg pentoxifyline (3% gel).

EXPERIMENTAL

Regarding the dosing schedule, on day 1 of the study (Visit 1) a single dose of investigational drug (of each concentration) or placebo, were administered by intravaginal via using an applicator device (syringe).

Drug: Gel PKB171; Drug: Gel PKB171 placebo

PKB vaginal gel, at 200 mg pentoxifyline (4% gel).

EXPERIMENTAL

Regarding the dosing schedule, on day 1 of the study (Visit 1) a single dose of investigational drug (of each concentration) or placebo, were administered by intravaginal via using an applicator device (syringe).

Drug: Gel PKB171; Drug: Gel PKB171 placebo

Placebo for PKB171

EXPERIMENTAL

Placebo for PKB171 in Part A: dose-escalation and Part B: multiple-dose extension substudy

Drug: Gel PKB171; Drug: Gel PKB171 placebo

Interventions

Gel PKB171 DRUG

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.

Also known as: pentoxifyline gel

PKB vaginal gel, at 100 mg pentoxifyline (2% gel).; PKB vaginal gel, at 150 mg pentoxifyline (3% gel).; PKB vaginal gel, at 200 mg pentoxifyline (4% gel).; Placebo for PKB171

Gel PKB171 placebo DRUG

PKB vaginal gel at the MTD or placebo once every 24 hours for two consecutive days

Also known as: placebo gel

PKB vaginal gel, at 100 mg pentoxifyline (2% gel).; PKB vaginal gel, at 150 mg pentoxifyline (3% gel).; PKB vaginal gel, at 200 mg pentoxifyline (4% gel).; Placebo for PKB171

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects had to fulfil all the following criteria to be eligible for study entry:
• Understand and agree to the trial procedures and sign an informed consent form.
• Female volunteers aged between 18 and 45 years.
• Regular menstrual cycle (regardless of menstrual cycle length)\*
• \*Subjects were asked for the duration of their menstrual cycle and the date of last menstruation in order to identify the stage of their menstrual cycle between days 7 and 21, and depending on their menstrual cycle they were distributed over the three consecutive study periods (and also to have them identified for the extension substudy).
• Medical records and physical examination showing no organic or psychiatric disorders.
• Gynaecological examination with visual inspection by the gynaecologist to rule out possible signs/symptoms of inflammation or vaginal infection and/or other gynaecological diseases, such as vulvovaginitis, infectious vulvovaginitis, candidal vulvovaginitis or fungal infection, trichomoniasis, bacterial vaginosis, irritative vulvovaginitis (due to the use of vaginal douching, deodorants, etc.), condylomata or genital warts, bartholinitis, cervicitis, etc. Symptoms: increased vaginal discharge and characteristics' change (colour, smell, texture and appearance) that varied according to the agent causing the infection, redness of the vulvar and vaginal mucosae, warts on the labia and/or anus, painful lump (with abscess), etc.
• In addition, during clinical examination, the gynaecologist asked volunteers about the presence of symptoms (pruritus or itching of the external genitalia and/or vagina, sensation of burning or stinging in the genitalia, urinary tract problems such as frequent urination, burning urination, heavy flow, etc.) to confirm the diagnosis.
• ECG, vital signs and blood and urine tests performed prior to the trial had to be within normal limits. Minor or one-off variations from the normal limits were allowed at the principal investigator's discretion, insofar as they do not pose a risk to subjects and do not interfere in the evaluation of the drug.
• Body mass index (BMI=weight/height2) should be between 18.5 and 24.99 kg/m2
• Women who have not participated in a clinical trial involving drugs in the three months prior to this study.
• Subjects had to fulfil all the following criteria to be eligible for study entry:
• Understand and agree to the trial procedures and sign an informed consent form.
• Female volunteers aged between 18 and 45 years.
• Regular menstrual cycle (regardless of menstrual cycle length)\*

You may not qualify if:

• Subjects who met any of the following conditions were not selected for this trial:
• Subjects who were not able to understand the nature of the trial and the procedures that they were asked to follow.
• History or clinical evidence of gastrointestinal, liver, renal or other types of disorders that led to a change in how the drug was absorbed, distributed, metabolised or excreted, or which suggested drug-induced gastrointestinal upset.
• History or clinical evidence of psychiatric disorders, alcoholism, abuse of medication or other drugs, or habitual consumption of psychoactive drugs.
• Any organic disease or major surgery in the 3 months prior to the start of the study.
• Subjects who had intolerance or serious adverse reactions to the study drugs or any of their ingredients.
• Smoking more than 5 cigarettes a day.
• Consuming more than 20 g of alcohol a day.
• Subjects with positive serology for hepatitis B, C or HIV.
• Women with a positive test for syphilis (RPR: rapid plasma reagin).
• Pregnant or breast-feeding women.
• Women who did not commit to using reliable birth control during the study
• Women who had any contraindication specified in the summary of product characteristics of oral pentoxifylline.
• To be eligible, subjects had to agree to the following restrictions regarding diet, sex, drug use and exercise during the study:
• Did not perform any strenuous physical exercise in the 48 hours prior to the start of each session.

Sponsors & Collaborators

• Prokrea BCN, S.L.: lead
• TFS Trial Form Support: collaborator

Study Officials

• José M Palacios, MD

  ProkreaBCN, S.L.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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), 3% (150 mg) and 4% (200 mg). Three cohorts of 8 healthy female volunteers participated. 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. Safety and tolerability of each strength level and dose-escalation decisions. 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-adm were made based on the occurrence of drug-related adverse events (AEs). Multiple-dose extension substudy: The 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.

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: June 12, 2025
• Study Start: January 27, 2016
• Primary Completion: April 26, 2016
• Study Completion: September 21, 2016
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share