Last updated: 11/04/2018 04:26:54
A Dose Ascending, Study To Examine The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of GSK233705B.
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomised, double-blind, placebo-controlled, dose ascending, 2-cohort, parallel group study to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of twice-daily inhaled doses of GSK233705B formulated with the excipient Magnesium Stearate in COPD subjects for 7-days.
Trial description: GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for the treatment of chronic obstructive pulmonary disease. This is a randomised, double-blind, placebo-controlled, dose ascending, parallel group study to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of twice daily inhaled doses of GSK233705B for 7 days, in COPD subjects.
Primary purpose:
Diagnostic
Trial design:
Parallel Assignment
Masking:
Not applicable
Allocation:
Randomized
Primary outcomes:
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to follow-up (approximately 45 days)
Summary of mean systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Up to Day 7 (24 hours post-dose)
Summary of mean heart rate
Timeframe: Up to Day 7 (24 hour post dose)
Maximum value of SBP and DBP (0-4 hour) for the morning dose
Timeframe: Up to Day 7 (0-4 hour)
Maximum value of heart rate (0-4 hour) for the morning dose
Timeframe: Up to Day 7 (0-4 hour)
Weighted mean of SBP and DBP (0-4 hour) for the morning dose
Timeframe: Up to Day 7 (0-4 hour)
Weighted mean of heart rate (0-4 hour) for the morning dose
Timeframe: Up to Day 7 (0-4 hour)
Number of participants with abnormal 12-lead ECG findings
Timeframe: Up to Day 7 (24 hour post dose)
Maximum value (0–4 hour) for the morning dose of ECG parameters corrected according to Fredericia’s formula (QTcF) and corrected according to Bazett’s formula (QTc B)
Timeframe: Up to Day 7 (0-4 hour)
Weighted Mean (0–4 h) for the morning dose of ECG parameters QTcF and QTc B
Timeframe: Up to Day 7 (0-4 hour)
Summary of mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)
Timeframe: Up to Day 7 (24-hour post dose)
Number of participants who used rescue medication
Timeframe: Up to Day 7
Number of participants with abnormalities in chemistry data of clinical concern
Timeframe: Up to Day 7
Number of participants with abnormalities in hematology data of clinical concern
Timeframe: Up to Day 7
Summary of microscopy data for participants with abnormal urinalysis dipstick results
Timeframe: Up to Day 7 (pre dose)
Summary of mean (0–24 hour) and maximum (0–24 hour) heart rate measured using 24 hour using Holter ECG data
Timeframe: Up to Day 7
Secondary outcomes:
Plasma concentrations of GSK233705
Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Urine concentrations of GSK233705
Timeframe: Day 1 and 7 throughout 24 hours
Derived plasma PK parameters-area under the plasma concentration-time curve over the dosing interval (AUC0-tau)
Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived plasma PK parameters-area under concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-t)
Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK plasma parameters-area under concentration-maximum observed plasma concentration (Cmax)
Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived PK plasma parameters-area under concentration-time of maximum observed plasma concentration (T-max), half-life (T-half) and last time point where the concentration is above the limit of quantification (T-last)
Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Derived urine pharmacokinetic (PK) parameters-area under the plasma concentration-amount of drug excreted unchanged in urine (Ae)
Timeframe: Day 1 and 7 throughout 24 hours
Derived urine PK parameters-area under concentration-fraction of dose excreted unchanged in urine (Fe)
Timeframe: Day 1 and 7 throughout 24 hours
Derived urine PK parameters-area under concentration-renal clearance (Clr)
Timeframe: Day 1 and 7 throughout 24 hours
Interventions:
Enrollment:
23
Primary completion date:
2007-11-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
This study has not been published in the scientific literature.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
darotropium bromide
Collaborators
Not applicable
Study date(s)
March 2007 to October 2007
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
40 - 75 years
Accepts healthy volunteers
No
- Men or women who are between 40 and 75 years of age
- Female subjects must be of non-childbearing
- Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
- The subject has a positive pre-study alcohol screen.
Inclusion and exclusion criteria
Inclusion criteria:
- Men or women who are between 40 and 75 years of age
- Female subjects must be of non-childbearing
- Subject diagnosed with COPD
- Body Mass Index 18.0
- 32.0 kg/m2 (inclusive)
- Subject is a smoker or an ex-smoker
- Subject has post-bronchodilator (200µg salbutamol) FEV1 of = 40% to = 80% of predicted normal.
- Subject has FEV1/FVC < 0.7 post-bronchodilator (200µg salbutamol).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Subject is available to complete all study measurements and procedures.
- Subjects have a 24hour holter recording that is within normal limits and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
Exclusion criteria:
- Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
- The subject has a positive pre-study alcohol screen.
- The subject has a positive pre-study drug screen.
- History of alcohol/drug abuse or dependence within 12 months of the study: Abuse
- The subject has a positive pregnancy test.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Subject has tested positive for HIV
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 60 days or 5 half-lives
- Exposure to more than three new chemical entities (NCE) within 10 months prior to the first dosing day or one NCE within 3 months prior to the first dosing day.
- The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study.
- The subject has a known allergy or hypersensitivity to ipratropium bromide, atropine and any of its derivatives or milk protein/lactose.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
- Subject has prostate hypertrophy or narrow angle glaucoma
Trial location(s)
Location
GSK Investigational Site
HARDERWIJK, Netherlands, 3844 DG
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2007-11-10
Actual study completion date
2007-11-10
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.
Additional information about the trial
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