Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin Hydrochloride (HCL) Combination Capsule in Fasted State

NCT02052713 | Completed Phase 1

• 1 other identifier: 116897
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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 milligram (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 followed by a 28-day washout period both in fasted 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.

Conditions

Urologic Diseases

Keywords

dutasteride; tamsulosin; healthy subject; dutasteride and tamsulosin combination; combination capsule of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic (PK) profile of second generation dutasteride when co-administered with tamsulosin HCL relative to the commercial combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence

  PK parameters include: area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject (AUC \[0-t\]), and maximum observed concentration (Cmax) as data permit

  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-administered with second generation dutasteride relative to the currently available commercial dutasteride 0.5 mg + tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence

  PK parameters include: AUC\[0-t\]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC\[0-infinity\]) \[defaulting to AUC(0-t)

  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 (5)

• PK profile of dutasteride

  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

  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

  Baseline (screening) and up to 33 days.

• Incidence of adverse events (AEs)

  Up to 48 days

• Clinical laboratory parameter assessment as a measure of safety and tolerability

  Up to 33 days

Study Arms (2)

Sequence AB

EXPERIMENTAL

Subjects will receive Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 1 and Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCl 0.4 mg combination) in period 2 orally once daily under fasted condition.

Drug: Commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg; Drug: Second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination capsule

Sequence BA

EXPERIMENTAL

Subjects will be randomized to receive Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCl 0.4 mg combination) in period 1 and Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 2 orally once daily under fasted condition.\[dutasteride 0.5 mg and tamsulosin HCl 0.4 mg) in period 2 orally once daily under fasted condition.

Drug: Commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg; Drug: Second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination capsule

Interventions

Commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg DRUG

Commercially available, orange and brown, hard shell capsule, administered orally as a single dose on Day 1 under fasted condition.

Sequence AB; Sequence BA

Second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination capsule DRUG

Orange and brown, hard shell capsule, administered orally, as a single-dose on Day 1 under fasted condition.

Sequence AB; Sequence BA

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 QT interval corrected (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.
• Cytochrome P450 enzyme 2D6 (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%).

You may not qualify if:

• 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 GlaxoSmithKline (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 Digital Rectal Examination (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 Cytochrome P450 enzyme 3A4 (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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Belfast, BT9 6AD, United Kingdom

Location

Related Links

• Results for study 116897 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Urologic Diseases

Interventions

Tamsulosin

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2014
• First Posted: February 3, 2014
• Study Start: February 19, 2014
• Primary Completion: December 29, 2014
• Study Completion: December 29, 2014
• Last Updated: September 13, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)