Bioequivalence Study of Dutasteride Five 0.1 mg and One 0.5 mg Soft Gelatin Capsules in Healthy Male Volunteers

NCT01929330 | Completed Phase 1 DMC

• 1 other identifier: 117342
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine the bioequivalence of 5 x 0.1 milligram (mg) capsules compared to 1 x 0.5 mg capsule of dutasteride in healthy male subjects. The results of this study are expected to support registration applications for androgenetic alopecia (AGA) in Japan and other international markets.

Conditions

Alopecia

Keywords

Bioequivalence; Healthy Male Volunteers; Androgenetic Alopecia; Dutasteride; Safety; Tolerability

Outcome Measures

Primary Outcomes (1)

• Serum pharmacokinetic (PK) parameters: maximum observed concentration (Cmax) and Area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject (AUC[0-t]) for dutasteride

  Serum PK samples will be collected pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48, and 72 hours post dose for both treatment periods

  From pre-dose up to 72 hrs

Secondary Outcomes (2)

• Time to Cmax (tmax) for dutasteride as data permit

  From pre-dose up to 72 hrs

• Safety and tolerability of all treatments as assessed by vital signs, electrocardiogram (ECG) measurements, review of adverse events (AEs) and clinical laboratory safety data

  From screening till Follow-up visit (10-14 days post-last dose)& 50-54 days post-last dose

Study Arms (2)

Sequence AB

EXPERIMENTAL

Subjects will be hospitalized to the clinical unit on the evening of Day -1. All subjects will receive 1 x 0.5mg oral dose of dutasteride (Sequence A), in the morning; Subjects will remain in the clinical unit until completion of all assessments at 24 hours post-dose on Day 2 including collection of the 24 hour post-dose PK sample. Subjects will return to the unit for the remaining PK samples at 36, 48 and 72 hours. The subject will receive or 5 x 0.1mg oral dose of dutasteride (Sequence B) in similar fashion as that of Sequence A. The two treatment sequences will be separated by a minimum washout period of 28 days to ensure that dutasteride is effectively eliminated from the subject between dosing occasions.

Drug: GI198745 0.1 mg; Drug: GI198745 0.5 mg

Sequence BA

EXPERIMENTAL

Subjects will be hospitalized to the clinical unit on the evening of Day -1. All subjects will receive 5 x 0.1mg oral dose of dutasteride (Sequence B) in the morning; Subjects will remain in the clinical unit until completion of all assessments at 24 hours post-dose on Day 2 including collection of the 24 hour post-dose PK sample. Subjects will return to the unit for the remaining PK samples at 36, 48 and 72 hours. The subjects will receive 1 x 0.5mg oral dose of dutasteride (Sequence A) in similar fashion as that of Sequence B, The two treatment sequences will be separated by a minimum washout period of 28 days to ensure that dutasteride is effectively eliminated from the subject between dosing occasions.

Drug: GI198745 0.1 mg; Drug: GI198745 0.5 mg

Interventions

GI198745 0.1 mg DRUG

It is available as soft gelatin capsule to be administered as 5 X 0.1 mg capsules as single oral dose with approximately 250 mL of water.

Sequence AB; Sequence BA

GI198745 0.5 mg DRUG

It is available as soft gelatin capsule to be administered as 1 X 0.5 mg capsules as single oral dose with approximately 250 mL of water.

Sequence AB; Sequence BA

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 within the range 19 - 32 kg/square meter (m2) (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.
• Willing and able to give written informed consent, which includes compliance with all the requirements and restrictions listed in the consent form for the full duration of the study, and able to understand and follow instructions related to study procedures.
• Able to swallow and retain oral medication.
• Alanine aminotransferase, Aspartate aminotransferase, alkaline phosphatase and bilirubin \<= 2.0 x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF) \< 450 milliseconds.
• 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 regular alcohol consumption within 6 months of the study defined as:
• An average weekly intake of \>21 units for males. In Australia one unit (=standard drink) is equivalent to 10 gram of alcohol: 270 milliliter (mL) of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250mL pre-mix full strength spirit (5%), 100 mL of wine (13.5%) and 30 mL of spirit (40%).
• 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 GSK Medical Monitor, contraindicates their participation.
• History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident prior to Screening visit;
• 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; 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.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Publications (1)

• Fossler MJ, Collins DA, Ino H, Sarai N, Ravindranath R, Bowen CL, Burns O. Evaluation of bioequivalence of five 0.1 mg dutasteride capsules compared to one 0.5 mg dutasteride capsule: a randomized study in healthy male volunteers. J Drug Assess. 2015 Jul 14;4(1):24-9. doi: 10.3109/21556660.2015.1067219. eCollection 2015.

  PMID: 27536459 DERIVED

Related Links

• Results for study 117342 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Alopecia

Interventions

Dutasteride

Condition Hierarchy (Ancestors)

Hypotrichosis; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic 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: August 22, 2013
• First Posted: August 27, 2013
• Study Start: September 23, 2013
• Primary Completion: January 9, 2014
• Study Completion: January 9, 2014
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)