Comparative Bioavailability of Two Fixed Dose Combination (FDC) Formulations of Dutasteride and Tamsulosin Hydrochloride Relative to Co-administration of Dutasteride With Tamsulosin Hydrochloride in Healthy Male Subjects Under Fed and Fasted States

NCT02184585 | Completed Phase 1

• 1 other identifier: 117057
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be an open-label, randomized, single dose, three way crossover study in healthy male subjects. The aim of the study is to evaluate the pharmacokinetic parameters of two formulations of a fixed dose combination (FDC) capsule of dutasteride and tamsulosin hydrochloride (HCl) (0.5 milligram \[mg\]/0.2 mg) relative to co-administration of dutasteride 0.5 mg capsules and tamsulosin hydrochloride 0.2 mg tablets in both the fed and fasted states. Approximately 84 healthy adult male subjects will be enrolled into the study and split into two cohorts (fed and fasted), allowing for approximately 36 subjects to complete each cohort. Subjects from both cohorts will receive single oral doses in 3 treatment periods and be randomized to one of six different treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) wherein A= FDC1: Dutasteride and tamsulosin HCl (0.5 mg/0.2 mg), B= FDC2: Dutasteride and tamsulosin HCl (0.5 mg/0.2 mg), C= Co-administration of commercial formulations of dutasteride(0.5mg) and tamsulosin HCl (0.2mg). Each treatment period will be separated by a minimum 28 day washout period. Blood samples for pharmacokinetic analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of blood pressure, heart rate and review of adverse events.

Conditions

Prostatic Hyperplasia

Keywords

bioavailability; crossover design; healthy male volunteers; tamsulosin hydrochloride; Dutasteride

Outcome Measures

Primary Outcomes (4)

• Area under the curve from 0 to the time of the last quantifiable concentration (AUC[0-t]) of tamsulosin in serum

  Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-t).

  Pre-dose and post dose at 15 minutes (min), 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours (h).

• Area under the curve from 0 to infinity (AUC[0-infinity]) of tamsulosin in serum

  Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-infinity).

  Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose.

• Maximum drug concentration (Cmax) of dutasteride in serum

  Relative bioavailability of dutasteride will be assessed by evaluating Cmax

  Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose.

• AUC(0-t) of dutasteride in serum

  Relative bioavailability of dutasteride will be assessed by evaluating AUC(0-t)

  Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose.

Secondary Outcomes (6)

• Time to reach maximum serum concentration (tmax) of tamsulosin and dutasteride in serum

  Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose

• Terminal half-life (t½) of tamsulosin in serum (as data permit).

  Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose

• Safety and tolerability as assessed by Vital signs (blood pressure and pulse rate [PR])

  Up to Day 110

• Safety and tolerability as assessed by electrocardiogram (ECG) measurements

  Up to Day 110

• Safety and tolerability as assessed by review of adverse events (AEs)

  Up to Day 110

Study Arms (2)

Cohort 1: Fasted state

EXPERIMENTAL

Treatment will be administered orally to 42 subjects in the fasted state. Subjects will be required to fast overnight (minimum 10 hours) and for a minimum of 4 hours after each dose. Subjects will participate in 3 treatment periods and assigned to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) in accordance with the randomization schedule generated by Clinical Statistics. The three treatment periods will be separated by a minimum washout period of 28 days

Drug: Treatment sequence A; Drug: Treatment sequence B; Drug: Treatment sequence C

Cohort 2 : Fed state

EXPERIMENTAL

Treatment will be administered orally to 42 subjects in the fed state (high fat breakfast). Dosing will take place within 30 minutes of the start of the meal. Subjects will participate in 3 treatment periods and assigned to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) in accordance with the randomization schedule generated by Clinical Statistics. The three treatment periods will be separated by a minimum washout period of 28 days

Drug: Treatment sequence A; Drug: Treatment sequence B; Drug: Treatment sequence C

Interventions

Treatment sequence A DRUG

FDC 1 - Fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg). Each capsule will contain dutasteride (0.5 mg) (CJ) and tamsulosin pellets (0.2 mg) version 1.

Cohort 1: Fasted state; Cohort 2 : Fed state

Treatment sequence B DRUG

FDC 2 - Fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg). Each capsule will contain dutasteride (0.5 mg) (CL) and tamsulosin pellets (0.2 mg) version 2.

Cohort 1: Fasted state; Cohort 2 : Fed state

Treatment sequence C DRUG

Co-administration of dutasteride 0.5 mg capsule (Oblong, size 6, dull yellow capsules: Commercially available) and tamsulosin hydrochloride 0.2 mg tablet (White, round standard convex tablet: Commercially available).

Cohort 1: Fasted state; Cohort 2 : Fed state

Eligibility Criteria

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

You may qualify if:

• Males aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 18 - 32 kg/m\^2 (square meter) (inclusive).
• Male subjects with female partners of child-bearing potential must agree to use a condom. This criterion must be followed from the time of the first dose of study medication until 50 days post-last dose.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Able to swallow and retain oral medication.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2x (Upper limit of normal) ULN; alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Based on single or averaged corrected QT (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 milliseconds (msec)
• Criteria Based Upon Medical Histories
• 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 allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
• 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 regular alcohol consumption within 6 months of the study defined for US sites as: 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 diabetes or peptic ulcer disease which is uncontrolled by medical management.
• History of breast cancer or clinical breast examination finding suggestive of malignancy. History of 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. Note: The investigator should make every appropriate effort to exclude the possibility of prostate cancer, including consideration of prostate biopsy in any subject with a known abnormal PSA.
• Criteria Based Upon Diagnostic Assessments

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 117057 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Prostatic Hyperplasia

Condition Hierarchy (Ancestors)

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

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: July 3, 2014
• First Posted: July 9, 2014
• Study Start: July 10, 2014
• Primary Completion: February 23, 2015
• Study Completion: February 23, 2015
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)