Last updated: 11/07/2018 10:07:25
Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in Fed State
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Single-Dose, Randomised, Open-Label, Two-Period Crossover Study to Determine the Bioequivalence of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in the Fed State in Healthy Adult Male Subjects
Trial description: The purpose of this study is to assess the bioequivalence of the second generation dutasteride and tamsulosin hydrochloride (HCL) combination capsule versus currently available commercial combination of dutasteride 0.5 milligrams (mg) and tamsulosin HCL 0.4 mg capsule in healthy adult male subjects. Subjects in this study will receive either a single oral dose of the second generation dutasteride 0.5 mg and tamsulosin 0.4 mg combination capsule or a single dose of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg capsule followed by a 28-day washout period both in fed state. The study will enroll approximately 92 healthy adult male subjects in order to complete approximately 76 evaluable subjects. The total duration of a subject's involvement in this study is anticipated to be approximately 12 weeks.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Pharmacokinetic profile for second generation dutasteride when co-administered with tamsulosin HCL relative to the currently available commercial combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
Timeframe: PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Composite of PK parameters for tamsulosin HCL when it is co-adminstered with second generation dutasteride relative to the currently available commercial dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
Timeframe: PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Secondary outcomes:
PK profile of dutasteride
Timeframe: PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
PK profile of tamsulosin HCL
Timeframe: PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Clinically significant changes in Vital signs measurements to assess safety and tolerability
Timeframe: Baseline (screening) and up to 33 days.
Incidence of adverse events (AEs)
Timeframe: Up to 48 days
Clinical laboratory parameter assessment as a measure of safety and tolerability
Timeframe: Up to 33 days
Interventions:
Enrollment:
77
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Renee Kurczewski; Chet Bowen; David Collins; John Zhu; Gulyeter Serbest, Michael Manyak. A Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule is Bioequivalent to Commercially Available Duodart ®. Clin Pharmacol Drug Devel. 2017;6(5):508-516.
Medical condition
Urologic Diseases
Product
dutasteride, dutasteride/tamsulosin, tamsulosin
Collaborators
Not applicable
Study date(s)
February 2014 to January 2015
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 50 years
Accepts healthy volunteers
Yes
- Males who are 18 to 50 years of age, inclusive.
- Weight range 55 to 95 kg (inclusive) and body mass index (BMI) 18 to 30 kilogram/meter^2 (kg/m^2) (inclusive).
- History of postural hypotension, dizziness, poor hydration, vertigo, vaso-vagal reactions or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
- History of any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with a subject’s safety, or interfere with the subject’s ability to follow indications or study procedures, or the interpretation of study results or obtaining informed consent or compliance to study procedures in the opinion of the Investigator or GSK Medical Monitor.
Inclusion and exclusion criteria
Inclusion criteria:
- Males who are 18 to 50 years of age, inclusive.
- Weight range 55 to 95 kg (inclusive) and body mass index (BMI) 18 to 30 kilogram/meter^2 (kg/m^2) (inclusive).
- Healthy subjects defined as individuals who are free from clinically significant illness or disease as determined by the investigator based on their medical history, physical examination, vital signs, laboratory studies, and electrocardiograms (ECGs).
- Single QTc <450 millisecond (msec) or QTc <480 msec in subjects with Bundle Branch Block, no clinically relevant abnormal finding on the screening ECG.
- Serum creatinine <1.5 x upper limit of normal (ULN) at screening.
- CYP2D6 Extensive Metabolizers only at screening
- Willing and able to give written informed consent
- Able to swallow and retain oral medication.
- Male subjects with female partners of child-bearing potential must agree to use 1 of the contraception methods.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), and bilirubin <=1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Exclusion criteria:
- History of postural hypotension, dizziness, poor hydration, vertigo, vaso-vagal reactions or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
- History of any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with a subject’s safety, or interfere with the subject’s ability to follow indications or study procedures, or the interpretation of study results or obtaining informed consent or compliance to study procedures in the opinion of the Investigator or GSK Medical Monitor.
- History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident prior to Screening visit; or diabetes or peptic ulcer disease which is uncontrolled by medical management.
- History of breast cancer or clinical breast examination finding suggestive of malignancy, malignancy within the past 5 years, except for basal cell carcinoma of the skin. Subjects with a prior malignancy who have had no evidence of disease for at least the past 5 years are eligible.
- Prior medical history or evidence of prostate cancer. Subjects with suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6 months and stable prostate specific antigen (PSA) are eligible for the study.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- Positive human immunodeficiency virus (HIV) test at screening.
- Use of prescription or non-prescription drugs.
- Strong CYP3A4 inhibitors (e.g. ketoconazole) and/or strong CYP2D6 inhibitors (e.g. paroxetine) usage throughout the study.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of regular alcohol consumption exceeding 21 drinks/week for men (1 unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 millilitre [mL]) of beer, 1 glass (equivalent to 125 mL) of wine or 1 (equivalent to 25 mL) measure of spirits) within 6 months of screening. Subjects must be able and willing to abstain from beverages and foods containing alcohol 24 hours prior to the first dose of study medication and until the completion of the final PK sample during each period.
- A positive urine drug or alcohol screen result at screening and at Day -1. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines.
- Subjects must be able and willing to stop using of any tobacco or nicotine containing products 24 hours prior to each dose and for the duration of confinement. At the discretion of the Investigator, light smokers (smoking <=10 cigarettes a day) would be considered for the study inclusion.
- The subject has received an investigational product or participated in any other research trial within 6 months or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication or anytime during the study period, exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Previous donation of blood or blood products in excess of 500 mL within a 90 day prior to the first dose of investigational products and the subject agrees not to donate blood during this study.
- History or presence of allergy, intolerance, contraindication or sensitivity to alpha blockers (e.g., tamsulosin), or 5 alpha reductase inhibitors (e.g., dutasteride) or drugs of these therapeutic classes, soya or peanuts, or any ingredients of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg, or a history of drug or other allergy (including true sulfonamide allergy) that, in the opinion of the investigator, contraindicates your participation in the study.
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
2015-02-01
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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Additional information
Results for study 116108 can be found on the GSK Clinical Study Register.
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