Bioavailability Study of Fixed Dose Combination (FDC) Dutasteride and Tamsulosin Hydrochloride (HCl) Relative to One Dutasteride and One Tamsulosin HCl Tablet in Healthy Male Subjects

NCT02509104 | Completed Phase 1

• 1 other identifier: 201897
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the bioavailability of a FDC capsule formulation of dutasteride and tamsulosin hydrochloride (0.5 milligram \[mg\]/0.2 mg) relative to coadministration of one dutasteride 0.5 mg capsule and one tamsulosin HCl 0.2 mg tablet in healthy male subjects in fed and fasted states. This is an open-label, randomized, single dose, two-way crossover study enrolling healthy male subjects, split into fasted (Cohort 1) and fed (Cohort 2) conditions. In both cohorts, one FDC capsule formulation of dutasteride 0.5 mg/tamsulosin HCl 0.2 mg will be administered in one treatment period and the coadministration of dutasteride and tamsulosin hydrochloride in a different treatment period. Each subject enrolled will be allowed to participate in only one cohort (i.e, will receive treatment under fasted or fed conditions) and will participate in both treatment periods. The two treatment periods will be separated by a minimum washout period of 28 days. The total duration in the study for each subject will be approximately 2.5 months from screening to the final follow-up visit.

Conditions

Prostatic Hyperplasia

Keywords

Bioavailability; Dutasteride; Healthy Male Subjects; Fixed Dose Combination

Outcome Measures

Primary Outcomes (2)

• Maximum observed serum concentration (Cmax) for dutasteride and tamsulosin

  Blood samples for PK analysis will be collected for each subject at the following time points: Pre-dose, 15 minutes (min), 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48 \& 72 hours post dose in both the treatment periods. Cmax will be determined for tamsulosin and dutasteride.

  Days 1 to 4 of both treatment periods

• Area under the serum concentration-time curve (AUC) zero to time 't' (AUC[0-t]) for tamsulosin and dutasteride; AUC 0 to infinity (AUC 0-inf) will be determined for tamsulosin as data permit

  Blood samples for PK analysis will be collected for each subject at the following time points: Pre-dose, 15 minutes (min), 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48 \& 72 hours post dose in both the treatment periods. AUC 0-t will be determined for tamsulosin and dutasteride. Additionally, AUC 0-inf will be determined for tamsulosin as data permit.

  Days 1 to 4 of both treatment periods

Secondary Outcomes (5)

• Time of occurrence of Cmax (Tmax) for dutasteride and tamsulosin

  Days 1 to 4 of both treatment periods

• Terminal phase half-life (t1/2) for tamsulosin

  Days 1 to 4 of both treatment periods

• Number of participants with adverse events (AE) /serious adverse event (SAE) as a measure of safety and tolerability

  From start of study treatment until follow-up contact (up to Week 7)

• Composite of vital signs as a measure of safety and tolerability

  Screening visit, Day -1, and Day 2 (in both treatment periods) and follow-up visit (up to 2.5 months).

• Composite of 12-lead electrocardiogram (ECG) assessment as a safety measure

  Screening, Day 1 and Day 2 in both treatment periods and follow-up visit (up to 2.5 months).

Study Arms (2)

Cohort 1 Fasted condition

EXPERIMENTAL

Each subject will receive both treatments A and B in either of period 1 or 2 with a washout period of 28 days between treatment periods. Subjects will receive the study treatments under fasting conditions.

Drug: FDC capsule of dutasteride and tamsulosin; Drug: Dutasteride soft gelatine capsule and tamsulosin HCl oral disintegrating tablet

Cohort 2 Fed condition

EXPERIMENTAL

Each subject will receive both treatment A and B in either of period 1 or 2 with a washout period of 28 days between treatment periods. Subjects will receive the study treatments under fed (high fat breakfast) conditions.

Drug: FDC capsule of dutasteride and tamsulosin; Drug: Dutasteride soft gelatine capsule and tamsulosin HCl oral disintegrating tablet

Interventions

FDC capsule of dutasteride and tamsulosin DRUG

Each FDC capsule contains a mixture of dutasteride formulation (equivalent to 0.5 mg dutasteride) and tamsulosin (equivalent to 0.2 mg tamsulosin) and its physical appearance is hard shell capsule.

Cohort 1 Fasted condition; Cohort 2 Fed condition

Dutasteride soft gelatine capsule and tamsulosin HCl oral disintegrating tablet DRUG

Coadministration of dutasteride soft gelatine capsule and tamsulosin HCl oral disintegrating tablet. Each soft gelatine capsule consist of 0.5 mg of dutasteride and physical appearance is Oblong, size 6, dull yellow capsule. Each oral disintegrating tablet consist of 0.2 mg of tamsulosin and its physical appearance is white, round standard convex.

Cohort 1 Fasted condition; Cohort 2 Fed condition

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

You may not qualify if:

• Body weight \>= 50 kilogram (kg) and body mass index (BMI) within the range 18 to 30 kg per meter square (m\^2) (inclusive).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
• Alanine aminotransferase (ALT) and bilirubin \>1.5xUpper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
• 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 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 diabetes or peptic ulcer disease which is uncontrolled by medical management.
• Current or history of: Breast cancer or clinical breast examination finding suggestive of breast malignancy; Malignancy within the past five 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 (e.g., positive biopsy, or suspicious ultrasound, or suspicious digital rectal examination \[DRE\]). Patients 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.
• Based on averaged corrected QT (QTc) values of triplicate ECGs obtained over a brief recording period: QTcF \> 450 millisecond (msec).
• Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the Study.
• History of regular alcohol consumption within 6 months of the study defined as: For United States sites: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 millilitre \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• 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 investigator or Medical Monitor, contraindicates their participation.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen.
• A positive test for human immunodeficiency virus (HIV) antibody.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Burns O, Zhu J, Manyak MJ, Ravindranath R, Koosha F, Haque N, Chung S. Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2018 May;7(4):422-434. doi: 10.1002/cpdd.380. Epub 2017 Aug 11.

  PMID: 28800206 DERIVED

Related Links

• Results for study 201897 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Prostatic Hyperplasia

Interventions

Dutasteride; Tamsulosin

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: July 27, 2015
• Study Start: July 30, 2015
• Primary Completion: October 10, 2015
• Study Completion: October 10, 2015
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)