Primary ObjectiveTo assess the absolute bioavailability of aluminium in healthy female subjects after topical application.Secondary Objectives-To explore the impact of shaving of the axilla on the dermal bioavailability of aluminium;-To explore the…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
general health
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / safety endpoints
Assessment of adverse events and local tolerability.
Pharmacokinetic endpoints
Assessment of the pharmacokinetics (PK) after topical application of 26AI, as
[26Al]-ACH, and IV administration of 26AI, as [26Al]-AlCl3 in citrate-buffered
physiological NaCl solution.
Secondary outcome
Not applicable
Background summary
Antiperspirants are widely used in the western world and many products contain
(water soluble) aluminium chlorohydrate (ACH). Currently, the databank on
biokinetics of ACH in man is very limited and there are no solid data available
on the dermal penetration of ACH. For assessment of the safety of aluminium
(Al) as a cosmetic ingredient in e.g. antiperspirants, the dermal
bioavailability is a crucial parameter. The dermal bioavailability is the
fraction of the topically applied Al that passes the various layers of the skin
to reach the systemic circulation. The fraction absorbed is determined by the
absorption rate of Al in relation to the rate of removal of Al due for instance
to loss of dead skin layers, perspiration, washing and shaving. Thus, personal
care habits may influence the amount of Al absorbed.
Past estimates of the bioavailability of Al have been based on conservative
default assumptions, animal studies, ex vivo human skin penetration studies.
All of these have their specific limitations. Moreover, personal care products
such as antiperspirants are typically used frequently, and not much is known
about how repeated dosing influences bioavailability. Therefore, there is a
growing need, also for regulatory authorities, for establishing a more reliable
estimate of the dermal bioavailability of Al under realistic consumer
conditions.
Study objective
Primary Objective
To assess the absolute bioavailability of aluminium in healthy female subjects
after topical application.
Secondary Objectives
-To explore the impact of shaving of the axilla on the dermal bioavailability
of aluminium;
-To explore the impact of regular product use on the dermal bioavailability of
aluminium.
Study design
This will be a single centre, open-label, randomized, longitudinal cross-over
study during which single doses of 26AI will be administered during each
treatment period (4).
Intervention
Deodorant met gelabeled aluminum en intraveneuze toediening van gelabeled
aluminum
Study burden and risks
In this study, 100 ng of [26AI]-AlCl3 in citrate buffered saline will be
administered intravenously. Normal plasma aluminium concentration is believed
to be 1 to 2 ug/L and, mostly within one week, greater than 95% of aluminium is
eliminated by the kidney; ~2% in bile. To minimize the risk for
hypersensitivity reactions, persons who have a history of an allergy for
aluminium will be excluded from study participation as a precautionary measure.
Other risks to subjects mainly relate to the IV injection and venous blood
sampling. lntravenous injection and the use of canulas (1 canula for IV
injection and 1 canula for venous blood sampling) are known to carry a small
risk of infection and hematoma.
All study product administrations will be performed in the clinic under medical
supervision. The subjects receiving any study product will remain in the
clinical unit for approximately 24 hours after each study product
administration.
The Nuclear Research and Consultancy Group (NRG) has calculated the radiation
burden of [26Al] as a result of participation in the study, 0.001 mSv, hereby
declaring the safety of this low dose of radioactivity to volunteers
Utrechtseweg 48
Zeist 3704 HE
NL
Utrechtseweg 48
Zeist 3704 HE
NL
Listed location countries
Age
Inclusion criteria
1. Healthy female subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis;
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive;
3. Able to communicate well with the investigator in the Dutch language;
4. Able to participate and willing to give written informed consent and to comply with the study restrictions;
5. Subjects should be used to frequent wet shaving with an appropriate female safety razor (electric shaving is not allowed, frequent defined as at least three times a week);
6. Sufficient venous access to allow blood sampling as per protocol.
Exclusion criteria
1. Any clinically significant abnormality as determined by medical history taking and physical examinations obtained during the screening visit that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;
2. A positive pregnancy test and/or nursing at screening;
3. Use of aluminium-containing medications within 21 days prior to investigational product administrations, or less than 5 half-lives, whichever is longer, and during the course of the study;
4. Treatment for diabetes, hypertension, coronary heart disease, psychiatric conditions, inflammatory chronic disease - rheumatoid arthritis, Crohn*s disease, ulcerous colitis, chronic constipation, eating disorders, or any disease condition which interferes with ADME of the investigational product within 21 days prior to investigational product administrations, or less than 5 half-lives, whichever is longer, and during the course of the study;
5. Reported menopausal state at screening, or posthysterectomy;
6. Known allergy for aluminium;
7. Axillary hyperhydrosis;
8. Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings at screening that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;
9. Participation in an investigational drug study within 3 months prior to screening or more than 4 times in the past year;
10. Any psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol;
11. History of alcohol or illicit drug abuse (alcohol abuse defined as alcohol consumption > 28 units/week);
12. Donation of blood within 3 months prior to screening or donation of plasma within 14 days prior to screening;
13. Not having a general practitioner;
14. Not willing to accept information transfer which concerns participation in the study, or information regarding health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner;
15. Not willing to give permission to have the general practitioner to be notified upon participation in this study;
16. Not willing to use effective (double barrier) contraception until at least 3 months after last investigational product administration;
17. Subjects who are part of the site staff of TNO or CHDR.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49088.028.14 |