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

This study has been completed.
Sponsor:
Information provided by:
PhotoCure
ClinicalTrials.gov Identifier:
NCT01050309
First received: January 14, 2010
Last updated: NA
Last verified: January 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics
Drug: hexaminolevulinate (HAL)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by PhotoCure:

Primary Outcome Measures:
  • To determine the extent of systemic absorption of HAL following vaginal and enema administration compared to intravenous administration to healthy female volunteers. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Designated as safety issue: No ]

Estimated Enrollment: 8
Study Start Date: November 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cervix 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
Active Comparator: colon 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
Active Comparator: Intravenous 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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050309

Locations
Netherlands
Pra-Eds-Nl
Zuidlaren, Netherlands, 9471
Sponsors and Collaborators
PhotoCure
Investigators
Study Director: Berit Nicolaisen, M.Sc. Photocure ASA
  More Information

No publications provided

Responsible Party: Berit Nicolaisen/Project Director, Photocure ASA
ClinicalTrials.gov Identifier: NCT01050309     History of Changes
Other Study ID Numbers: PC CO102/09
Study First Received: January 14, 2010
Last Updated: January 14, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Aminolevulinic Acid
Dermatologic Agents
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014