An Open-label, Single-dose, Three Period Study to Determine the Pharmacokinetic Parameters of Hexaminolevulinate (HAL) Hydrochloride After Vaginal, Enema and Intravenous Administration of Healthy Female Volunteers

Pharmacokinetics Clinical Trial

Official title:

An Open-label, Single-dose, Three Period Study to Determine the Pharmacokinetic Parameters of Hexaminolevulinate (HAL) Hydrochloride After Vaginal, Enema and Intravenous Administration of Healthy Female Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01050309
• Other study ID #: PC CO102/09
• Status: Completed
• Phase: Phase 1
• First received: January 14, 2010
• Last updated: January 14, 2010
• Start date: November 2009
• Est. completion date: December 2009

Study information

• Verified date: January 2010
• Source: Photocure
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The study will determine the extent of systemic absorption of HAL following vaginal and enema administration compared to intravenous administration to healthy female volunteers.

In addition, the pharmacokinetic parameters for the combined level of 14C labelled substances (sum of parent and possible metabolites)will be assessed. The safety and tolerability of HAL following vaginal, enema and intravenous administration to healthy female volunteers will be investigated.

Description:

This is a single-centre, non-randomised, open-label, single-dose, three-period study planned to include eight healthy female volunteers. Subjects will attend a screening visit within 21 days of dosing. In Period 1, an intravenous dose of HAL 0.4 mg/kg including 100 nCi (3.7 kBq) 14C will be infused over a one hour period. In Period 2, a vaginal dose HAL 150 mg including 13,9 kBq of 14C HAL will be administered for 7 hours. In period 3, following a colon cleaning, 100mg HAL enema including 14,8 kBq of 14C will be instilled for 30 minutes in 8 subjects. Period 1, 2 and Period 3 will be conducted in an identical manner except that subjects will receive the HAL by different dose routes. Blood samples will be drawn during 3 days of follow up to evaluate the single dose pharmacokinetics of HAL for each dose route. In addition, urine and faeces will be collected from Period 1. The urine and faces samples will be stored for possible future analysis.

There will be a minimum of 7 days washout between the three dosing periods. Subjects will attend a final follow-up visit at the 14 day blood sampling visit in the third study period. The total amount of 14C-label used in each volunteer is estimated to be approximately 33.3 kBq. No formal calculation of the radiation burden was made. Based on data of full-dose ADME studies it is estimated that this dose will give a radiation burden of less than 0.01 mSv, which falls in ICRP category I: trivial risk.

Diagnosis and main criteria for inclusion:

Healthy female subjects aged 18 to 55 years (inclusive) with body mass index (BMI) >19 and <30 kg/m2 who give written informed consent and comply with all the inclusion and exclusion criteria, will be entered into the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• healthy women aged 18 to 55 years (inclusive)

• Body Mass Index (BMI) > 19 and < 30 kg/m2

• Able to understand the nature of the study and to give written informed consent

Exclusion Criteria:

• consumption of medication (including 'over the counter' preparations and herbal remedies) within two weeks of dosing. Simple analgesics (e.g. paracetamol) may be allowed at the discretion of the Investigator

• past or current drug exposure amounting to drug abuse or addiction

• past or current alcohol exposure amounting to alcohol abuse or addiction; [i.e. > 21 units per week for females, where 1 unit = one measure of spirit (25 ml), one glass of wine (125 ml) or ½ pint beer]

• smokers of more than five cigarettes a day

• donation of blood within two months before the study

• receipt of a 14C labelled compound in one year before the study

• participation in a clinical trial involving receipt of a licensed or unlicensed medicinal product within three months before the study

• unwilling or unable to comply with the study protocol for any reason

• positive test for hepatitis B surface antigen or hepatitis C antibody or human immunodeficiency virus (HIV) at screening

• subjects with childbearing potential (i.e. pre-menopausal, not surgically sterile) not willing to use a medically accepted contraceptive (oral contraception) regimen from the pre-study screening until at least 3 months after the last study period.

• pregnant or lactating women

• clinically relevant abnormalities in the pre-study screening.

• known allergy or intolerance to any compound in the test product or any other closely related compound

• any other acute or chronic disease which could influence the subject's health and/or the study results, e.g. porphyria

• clinically relevant abnormalities from standard gynecological examination (incl. cervical smear and determination of position of uterus)

• Irregular defecation pattern, i.e. less than once per 2 days

Study Design

Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• hexaminolevulinate (HAL)
Intravenous dose of HAL 0.4 mg/kg including 100 nCi (3.7 kBq) 14C infused over a one hour period. A vaginal dose HAL 150 mg including 13,9 kBq of 14C HAL will be administered for 7 hours. Following a colon cleaning, 100mg HAL enema including 14,8 kBq of 14C will be instilled for 30 minutes in colon

Locations

Country	Name	City	State
Netherlands	Pra-Eds-Nl	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Photocure

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the extent of systemic absorption of HAL following vaginal and enema administration compared to intravenous administration to healthy female volunteers.			No
Secondary	To determine pharmacokinetic parameters for the combined level of 14C labelled substances. To assess the safety and tolerability of HAL following vaginal, enema and intravenous administration to healthy female volunteers.			No