Clinical trial NCT03143166: Pradaxa Tablet Proton Pump Inhibitor (PPI) Bioavailability (BA) Study in Japan
Official title: Relative Bioavailability of Tablet Formulation of Dabigatran Etexilate With and Without Co-administration of Rabeprazole in Healthy Male Subjects (an Open-label, Single-dose, Two-period, Single-arm Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-alcoholic Fatty Liver Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-05-08
Enrollment: 36
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to investigate the relative Bioavailability (BA) of tablet formulation of Dabigatran etexilate (DE) with and without co-administration of rabeprazole in healthy male subjects.

The secondary objective is the evaluation and comparison of several pharmacokinetic parameters between the treatments.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
* Age ≥ 20 and ≤ 40 years at informed consent
* Body mass index (BMI) of 18 ≥ and ≤ 25 kg/m2 at screening
* Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria:

* Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
* Measurement of systolic blood pressure (BP) outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate (PR) outside the range of 45 to 90 bpm at screening
* Any laboratory value outside the reference range before administration of DE that the investigator considers to be of clinical relevance
* Any evidence of a concomitant disease judged as clinically relevant by the investigator
* Any relevant bleeding history considered by the investigator
* Any history or evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Any history of hypochlorhydria or achlorhydria
* Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
* Planned surgeries within four weeks following the end-of trial examination
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or relevant acute infections
* History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
* Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
* Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
* Inability to refrain from smoking at trial site
* Alcohol abuse (consumption of more than 30 g per day: e.g., 750 ml of beer, 1.5 gous \[equivalent to 270 mL\] of Sake)
* Drug abuse or positive drug screening
* Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
* Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
* Inability to comply with dietary regimen of trial site
* Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
measure: Maximum Concentration of Total Dabigatran in Plasma (Cmax).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
measure: Maximum Concentration of Free Dabigatran in Plasma (Cmax).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
measure: Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
measure: Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
timeFrame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Other outcomes:
Locations:
city: Fukuoka, Fukuoka
country: Japan
facility: Souseikai Hakata Clinic
Study officials:
References:
citation: Harada A, Ikushima I, Haranaka M, Yanagihara A, Nakayama D. Bioequivalence of a Newly Developed Dabigatran Etexilate Tablet Versus the Commercial Capsule and Impact of Rabeprazole-Induced Elevated Gastric pH on Exposure in Healthy Subjects. Am J Cardiovasc Drugs. 2020 Jun;20(3):249-258. doi: 10.1007/s40256-019-00377-x.