Pharmacokinetics of Different Formulations of Telmisartan, Amlodipine, and Hydrochlorothiazide (HCTZ) in Japanese Healthy Male Volunteers

Pharmacokinetics of Multiple Oral Doses of Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg Fixed-dose Combination Tablet, Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg Fixed-dose Combination Tablet and Telmisartan 80 mg/Amlodipine 5 mg Fixed-dose Combination Tablet at Steady State in Healthy Male Subjects: an Open-label, Randomised, Multiple-dose, Three Treatment, Three-period, Six-sequence Crossover Study

To assess drug drug interaction through pharmacokinetics investigation at steady state of Telmisartan, Amlodipine, and Hydrochlorothiazide (HCTZ) given as three different formulations in healthy Japanese male subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Telmisartan/Amlodipine/HCTZ; Drug: Telmisartan/Amlodipine; Drug: Telmisartan/HCTZ

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kanagawa , Yokohama, Japan
    • 1348.5.001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy Japanese male subjects age >=20 and <=35 years; body weight: >=50 kg and <=80 kg; body mass index: >=18.0 and <=25.0 kg/m2
• Without any clinically significant findings and complications on the basis of a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead electrocardiograms (ECGs), clinical laboratory tests
• Signed and dated written informed consent prior to admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation.

Exclusion criteria:

- Any finding of the medical examination (including BP, PR and ECGs) deviating from normal and of clinical relevance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T/A/H; Telmisartan/Amlodipine/HCTZ fixed-dose combination	Drug: Telmisartan/Amlodipine/HCTZ; Telmisartan/Amlodipine/HCTZ fixed-dose combination
Active Comparator: T/A; Telmisartan/Amlodipine fixed-dose combination	Drug: Telmisartan/Amlodipine; Telmisartan/Amlodipine fixed-dose combination
Active Comparator: T/H; Telmisartan/HCTZ fixed-dose combination	Drug: Telmisartan/HCTZ; Telmisartan/HCTZ fixed-dose combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Measured Concentration (Cmax) at Steady State for Telmisartan	Maximum measured concentration (Cmax) of telmisartan in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h and 72h after 10 days drug administration
Area Under the Plasma Concentration Curve at Steady State for Telmisartan	Area under the plasma concentration curve (AUC) of telmisartan in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h and 72h after 10 days drug administration
Maximum Measured Concentration (Cmax) at Steady State for Amlodipine	Maximum measured concentration (Cmax) of amlodipine in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h and 144h after 10 days drug administration
Area Under the Plasma Concentration Curve at Steady State for Amlodipine	Area under the plasma concentration curve (AUC) of amlodipine in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h and 144h after 10 days drug administration
Maximum Measured Concentration (Cmax) at Steady State for HCTZ	Maximum measured concentration (Cmax) of HCTZ in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h and 48h after 10 days drug administration
Area Under the Plasma Concentration Curve at Steady State for HCTZ	Area under the plasma concentration curve (AUC) of HCTZ in plasma at steady state over the dosing interval tau	15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h and 48h after 10 days drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of HCTZ Excreted in Urine at Steady State From 0 to 24 Hours	Amount of HCTZ excreted in urine over the time interval from 0 to 24 hours at steady state	0-6 hours (h), 6-12h and 12-24h after drug administration on day 10

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Hydrochlorothiazide; Telmisartan; Telmisartan amlodipine combination
• Other Study ID Numbers: 1348.5