Last updated: 11/07/2018 11:24:45
Characterization of Exposure from Topical Administration of [14C] Umeclidinium to Axilla or Palm of Healthy Male Subjects
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: Characterization of Exposure from Topical Administration of [14C] Umeclidinium to Axilla or Palm of Healthy Male Subjects
Trial description: The purpose of this study is to characterize the pharmacokinetics (PK), safety and tolerability of topically applied umeclidinium following single dose topical administration. The results from this study will be used to 1) improve our understanding of the risk of systemic accumulation upon chronic administration, 2) support dosing recommendations in a 2a/2b study for axillary administration and, potentially, a separate combined 2a/2b study for palmar administration, and 3) confirm whether the same formulation can be used for axillary and palmar application for the next studies.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
PK Assessment (Cmax) for [14C] umeclidinium and total radioactivity
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (tmax) for [14C] umeclidinium and total radioactivity
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (AUC) for [14C] umeclidinium and total radioactivity
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
PK Assessment (t1/2) for [14C] umeclidinium and total radioactivity
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Compartmental modeling of absorption rate for [14C] umeclidinium
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Compartmental modeling of elimination rate for [14C] umeclidinium
Timeframe: Day 1: Predose, 2, 4, 5, 6, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14 and 16 hrs postdose. Day 2: 24, 30 and 36 hrs. Day 3 (48 hours), Day 4 (72 hrs) and up to follow-up Day 14.
Secondary outcomes:
Determine the amount of Umeclidinium absorbed in the skin
Timeframe: Day 1 (and Day 2 if required)
Safety Assessment for AEs
Timeframe: From first dose up to Follow-up (Day 14)
Safety Assessment for ECGs, and telemetry
Timeframe: From Screening up to Follow-up (Day 14)
Safety Assessment for hematology laboratory parameters
Timeframe: From Screening up to Follow-up (Day 14)
Safety Assessment for measurement of blood pressure
Timeframe: From Screening up to Follow-up (Day 14)
Number of subjects with application site skin irritation
Timeframe: From Day 1 up to Follow-up (Day 14)
Safety Assessment for clinical chemistry laboratory parameters
Timeframe: From Screening up to Follow-up (Day 14)
Safety Assessment for measurement of pulse rate
Timeframe: From Screening up to Follow-up (Day 14)
Interventions:
Enrollment:
18
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
T Pene Dumitrescu, LL Santos, SC Hughes, AI Pereira, GC Young, E Hussey, P Charlton, S Baptiste-Brown, JS Stuart, V Vincent, SP van Marle, VD Schmith. A novel method for studying the pharmacokinetics of [14c]umeclidinium after application to the axilla or palm of healthy male subjects. Clin Transl Sci. 2016;9(4):183-191.
Medical condition
Hyperhidrosis
Product
umeclidinium bromide
Collaborators
Not applicable
Study date(s)
September 2013 to February 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
30 - 55 years
Accepts healthy volunteers
Yes
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring (including screening ECG and screening Holter monitoring). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with significant lab values outside the normal range should always be excluded from enrolment.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned. Subject is willing to provide informed consent.
- Subject is mentally or legally incapacitated.
- History of current significant medical illness including cardiovascular thrombotic events, myocardial infarction, stroke or other cardiac disease, hypertension, peptic ulcer disease or gastrointestinal bleeding, skin disorders, hematological disease, bronchospastic respiratory disease, asthma, diabetes mellitus, renal or hepatic insufficiency, or any other illness that the investigator deems clinically significant for exclusion of the subject from the study.
Inclusion and exclusion criteria
Inclusion criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring (including screening ECG and screening Holter monitoring). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with significant lab values outside the normal range should always be excluded from enrolment.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned. Subject is willing to provide informed consent.
- Axilla or palm size must be able to accommodate one of the 40 centimeter square (cm^2) templates and, as relevant for the cohort, the protective device.
- Axilla or palm must be free of tattoos, scar tissue or other tissue damage that could affect drug absorption or subject safety.
- Males between 30 and 55 years of age inclusive, at the time of signing the informed consent.
- Body Mass Index (BMI) within the range 18-27 kilogram per meter square (kg/m^2) (inclusive).
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the Protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
- Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Corrected QT interval using Fridericia formula (QTcF) <450 msec; or QTcF <480 milliseconds (msec) in subjects with Bundle Branch Block
Exclusion criteria:
- Subject is mentally or legally incapacitated.
- History of current significant medical illness including cardiovascular thrombotic events, myocardial infarction, stroke or other cardiac disease, hypertension, peptic ulcer disease or gastrointestinal bleeding, skin disorders, hematological disease, bronchospastic respiratory disease, asthma, diabetes mellitus, renal or hepatic insufficiency, or any other illness that the investigator deems clinically significant for exclusion of the subject from the study.
- Diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator or GSK medical monitor would prevent use of an anticholinergic and therefore study participation.
- A mean QTcF value at screening >450msec, the QTcF of all 3 screening ECGs are not within 10% of the mean, or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
- A history of elevated resting blood pressure or a mean blood pressure equal to or higher than 139/89 millimeters of mercury (mmHg) at screening or prior to dosing.
- A mean heart rate outside the range 40-100 beats per minute (bpm) at screening or prior to dosing.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other significant allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Unable or unwilling to avoid use of under-arm deodorant or topical creams/lotions etc. to axilla or palms (depending on the subject’s cohort) from admission on Day -1 until discharged from the unit (note washing with soap and water will be permitted on a daily basis once the topical agent has been removed from the application site).
- The radiation exposure from the previous 3 year period is over 10 millisievert (mSv) for any subject who has been exposed to ionizing radiation above background levels as a result of his work with radiation as a Category A (classified) worker or as a result of research studies in which he may have been involved.
- An occupation which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays within the past 12 months.
- Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. Each subject’s previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination / carryover into the current study.
- Subjects who have received a total body radiation dose of greater than 0.7 mSv or exposure to significant radiation (e.g. computed tomography [CT] scan) for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column) during work or during participation in a medical trial in the previous year.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 60 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- A positive pre-study drug/alcohol screen.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- History of smoking >= 5 cigarettes/day within the last year and any smoker who is unwilling or unable to refrain from smoking while participating in the clinical trial.
- History of regular alcohol consumption within 6 months of the study.
- Unable to refrain from consumption of red wine, Seville oranges, kumquat, satsuma, ugli, tangerine, tangelo, sprite, cassis, grapefruit or grapefruit juice and/or pummelos, other citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (if available, whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 60 day period.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2014-19-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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