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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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02183675
Enrollment
36
Registered
2014-07-08
Start date
2014-07-31
Completion date
2014-10-31
Last updated
2016-11-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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

Interventions

DRUGTelmisartan/Amlodipine

Telmisartan/Amlodipine fixed-dose combination

DRUGTelmisartan/Amlodipine/HCTZ

Telmisartan/Amlodipine/HCTZ fixed-dose combination

DRUGTelmisartan/HCTZ

Telmisartan/HCTZ fixed-dose combination

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
20 Years to 35 Years
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
Maximum Measured Concentration (Cmax) at Steady State for Amlodipine15 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 administrationMaximum measured concentration (Cmax) of amlodipine in plasma at steady state over the dosing interval tau
Maximum Measured Concentration (Cmax) at Steady State for Telmisartan15 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 administrationMaximum measured concentration (Cmax) of telmisartan in plasma at steady state over the dosing interval tau
Area Under the Plasma Concentration Curve at Steady State for Telmisartan15 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 administrationArea under the plasma concentration curve (AUC) of telmisartan in plasma at steady state over the dosing interval tau
Area Under the Plasma Concentration Curve at Steady State for HCTZ15 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 administrationArea under the plasma concentration curve (AUC) of HCTZ in plasma at steady state over the dosing interval tau
Area Under the Plasma Concentration Curve at Steady State for Amlodipine15 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 administrationArea under the plasma concentration curve (AUC) of amlodipine in plasma at steady state over the dosing interval tau
Maximum Measured Concentration (Cmax) at Steady State for HCTZ15 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 administrationMaximum measured concentration (Cmax) of HCTZ in plasma at steady state over the dosing interval tau

Secondary

MeasureTime frameDescription
Amount of HCTZ Excreted in Urine at Steady State From 0 to 24 Hours0-6 hours (h), 6-12h and 12-24h after drug administration on day 10Amount of HCTZ excreted in urine over the time interval from 0 to 24 hours at steady state

Countries

Japan

Participant flow

Recruitment details

An open-label, randomised, six-sequence crossover design. Each participant received three treatments each for 10 days. There was no washout period between treatments.

Participants by arm

ArmCount
T80-A5-H12.5 / T80-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5) * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
6
T80-H12.5 / T80-A5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
6
T80-A5 / T80-A5-H12.5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5) * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
6
T80-A5 / T80-H12.5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
6
T80-A5-H12.5 / T80-A5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5) * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
6
T80-H12.5 / T80-A5-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order: * Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) * Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5) * Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
6
Total36

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Treatment Period 2 (10 Days)Adverse Event000002

Baseline characteristics

CharacteristicT80-H12.5 / T80-A5-H12.5 / T80-A5TotalT80-A5-H12.5 / T80-H12.5 / T80-A5T80-H12.5 / T80-A5 / T80-A5-H12.5T80-A5 / T80-A5-H12.5 / T80-H12.5T80-A5 / T80-H12.5 / T80-A5-H12.5T80-A5-H12.5 / T80-A5 / T80-H12.5
Age, Continuous29.3 Years
STANDARD_DEVIATION 4.9
28.0 Years
STANDARD_DEVIATION 4.6
29.0 Years
STANDARD_DEVIATION 4.9
27.3 Years
STANDARD_DEVIATION 5.2
27.0 Years
STANDARD_DEVIATION 4.2
25.8 Years
STANDARD_DEVIATION 4.1
29.5 Years
STANDARD_DEVIATION 5.1
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
6 Participants36 Participants6 Participants6 Participants6 Participants6 Participants6 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
3 / 363 / 362 / 345 / 36
serious
Total, serious adverse events
0 / 360 / 360 / 340 / 36

Outcome results

Primary

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

Time frame: 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

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Area Under the Plasma Concentration Curve at Steady State for Amlodipine230 ng*h/mLGeometric Coefficient of Variation 23.4
T80-A5Area Under the Plasma Concentration Curve at Steady State for Amlodipine223 ng*h/mLGeometric Coefficient of Variation 21.8
90% CI: [100.167, 104.867]ANOVA
Primary

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

Time frame: 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

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Area Under the Plasma Concentration Curve at Steady State for HCTZ584 ng*h/mLGeometric Coefficient of Variation 23.8
T80-A5Area Under the Plasma Concentration Curve at Steady State for HCTZ565 ng*h/mLGeometric Coefficient of Variation 23.4
90% CI: [98.73, 108.28]ANOVA
Primary

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

Time frame: 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

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Area Under the Plasma Concentration Curve at Steady State for Telmisartan2510 ng*h/mLGeometric Coefficient of Variation 72.1
T80-A5Area Under the Plasma Concentration Curve at Steady State for Telmisartan2570 ng*h/mLGeometric Coefficient of Variation 70.8
T80-H12.5Area Under the Plasma Concentration Curve at Steady State for Telmisartan2580 ng*h/mLGeometric Coefficient of Variation 81.4
90% CI: [90.43, 105.19]ANOVA
90% CI: [96.94, 107.4]ANOVA
Primary

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

Time frame: 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

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Maximum Measured Concentration (Cmax) at Steady State for Amlodipine11.8 ng/mLGeometric Coefficient of Variation 21.8
T80-A5Maximum Measured Concentration (Cmax) at Steady State for Amlodipine11.3 ng/mLGeometric Coefficient of Variation 22.3
90% CI: [101.023, 106.964]ANOVA
Primary

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

Time frame: 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

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Maximum Measured Concentration (Cmax) at Steady State for HCTZ107 ng/mLGeometric Coefficient of Variation 28.5
T80-A5Maximum Measured Concentration (Cmax) at Steady State for HCTZ102 ng/mLGeometric Coefficient of Variation 28
90% CI: [99.23, 111.847]ANOVA
Primary

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

Time frame: 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

Population: Pharmacokinetic (PK) set which included all subjects in the treated set who had evaluable PK variable of test (T80/A5/H12.5 mg) and at least one of two references (T80/H12.5 mg and T80/A5 mg) for treatment periods 1, 2, and 3. Subjects who had a protocol deviation relevant to the evaluation of relative bioavailability were excluded.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Maximum Measured Concentration (Cmax) at Steady State for Telmisartan970 ng/mLGeometric Coefficient of Variation 69.3
T80-A5Maximum Measured Concentration (Cmax) at Steady State for Telmisartan857 ng/mLGeometric Coefficient of Variation 70.7
T80-H12.5Maximum Measured Concentration (Cmax) at Steady State for Telmisartan895 ng/mLGeometric Coefficient of Variation 75
90% CI: [93.081, 126.225]ANOVA
90% CI: [98.216, 134.326]ANOVA
Secondary

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

Time frame: 0-6 hours (h), 6-12h and 12-24h after drug administration on day 10

Population: PK set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
T80-A5-H12.5Amount of HCTZ Excreted in Urine at Steady State From 0 to 24 Hours10.4 mgGeometric Coefficient of Variation 11.4
T80-A5Amount of HCTZ Excreted in Urine at Steady State From 0 to 24 Hours9.9 mgGeometric Coefficient of Variation 12.2
90% CI: [101.949, 107.734]ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026