Steady State Pharmacokinetics of Telmisartan, Ramipril or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers

• ClinicalTrials.gov Identifier: NCT02215005
• Recruitment Status: Completed
• First Posted: August 13, 2014
• Last Update Posted: August 13, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: August 12, 2014
• First Posted Date: August 13, 2014
• Last Update Posted Date: August 13, 2014
• Study Start Date: June 2007
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2014)

• AUCτ,ss (area under the concentration-time curve in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• Cmax,ss (maximum measured concentration in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 72 hours after last drug administration of each treatment ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 12, 2014)

• Concentration of the analytes in plasma [ Time Frame: 2, 4, and 12 hours after administration of the first dose of each treatment on day 1 ]
• pre-dose concentration of the analytes in plasma immediately before the administration of the next dose [ Time Frame: pre-dose up to day 5 of each treatment ]
• tmax,ss (time from last dosing to the maximum concentration of the analytes in plasma at steady state) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• Cmin,ss (minimum concentration of the analytes in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• Cpre,ss (pre-dose concentration of the analytes in plasma immediately before the administration of the next dose at steady state) [ Time Frame: pre-dose up to day 5 of each treatment ]
• Cavg (average concentration of the analytes in plasma at steady state) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• λz,ss (terminal rate constant in plasma at steady state) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• t1/2, ss (terminal half-life of the analyte in plasma at steady state) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• CL/F,ss (apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• Vz/F,ss (apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• PTF (Peak-Trough Fluctuation) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• AUC0-tz,ss (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) [ Time Frame: up to 72 hours after last drug administration of each treatment ]
• Number of patients with adverse events [ Time Frame: up to day 76 ]
• Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse rate) [ Time Frame: up to day 76 ]
• Number of patients with clinically relevant changes in 12-lead electrocardiogram [ Time Frame: up to day 76 ]
• Number of patients with clinically relevant changes in laboratory tests [ Time Frame: up to day 76 ]
• Assessment of tolerability by the investigator on a 4-point scale [ Time Frame: Day 8 of each treatment ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Steady State Pharmacokinetics of Telmisartan, Ramipril or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers
• Official Title: Steady State Pharmacokinetics of 80 mg Telmisartan (Micardis®), 10 mg Ramipril (Delix®) or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers (an Open-label, Randomised, Multiple-dose, Three-way Crossover Study)
• Brief Summary: The main objective was to investigate the effect of concurrent dosing of 10 mg ramipril and 80 mg telmisartan on the multiple-dose pharmacokinetics of telmisartan and ramipril. Therefore the relative bioavailability of telmisartan and ramipril given in combination was determined in comparison with either telmisartan or ramipril given alone.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

• Drug: Telmisartan
  Other Name: Micardis®
• Drug: Ramipril
  Other Name: Delix®

Study Arms

• Experimental: Telmisartan + Ramipril
  5 days qd
  Interventions:

  • Drug: Telmisartan
  • Drug: Ramipril
• Active Comparator: Telmisartan
  5 days qd
  Intervention: Drug: Telmisartan
• Active Comparator: Ramipril
  5 days qd
  Intervention: Drug: Ramipril

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 12, 2014): 42
• Original Actual Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy males and females according to the following criteria based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
• Age ≥18 and ≤55 years
• Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial (especially unspecific inducing agents like St.John´s wort (Hypericum perforatum) or inhibitors like cimetidine) or drugs that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration of trial drug or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Alcohol abuse (more than 60 g/day) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration of trial drug or during the trial)
• Excessive physical activities (within one week prior to administration of trial drug or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hyperkalaemia, hypokalemia, family history of Long QT Syndrome)
• Any history of relevant low blood pressure
• Supine blood pressure at screening of systolic <110 mm Hg and diastolic <60 mm Hg
• History of urticaria
• History of angioneurotic edema
• Hereditary fructose intolerance
• Salt and/or volume depletion

For female subjects:

• Pregnancy or planning to become pregnant during the study or within 1 months of study completion
• Positive pregnancy test
• Not willing or unable to use a reliable method of contraception such as implants, injectables, combined oral contraceptives, sterilisation, intrauterine device, double barrier method, sexual abstinence for at least 1 month, or vasectomised partner as only method of contraception for at least 6 months prior to participation in the trial, during and up to 1 month after completion/termination of the trial
• Chronic use of oral contraception containing ethinyl estradiol as the only method of contraception
• Currently lactating

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02215005
• Other Study ID Numbers: 1236.6
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Boehringer Ingelheim
• Study Sponsor: Boehringer Ingelheim
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: August 2014