check_circleStudy Completed
Clinical Pharmacology
Bayer Identifier:
13785
ClinicalTrials.gov Identifier:
Not Available
EudraCT Number:
EU CT Number:
Not Available
Phase I Multiple dose escalation study
Trial purpose
Primary objective: To investigate the safety and tolerability of BAY 94-8862 after multiple oral doses of 10 mg twice a day (bid), 20 mg bid and 40 mg once a day given as 10 mg immediate release tablets over 10 days in 12 healthy male subjects (9-verum and 3 placebo) per dose step in a randomized, single-blind, placebo-controlled, group-comparison design.
Secondary objectives: To assess
- The pharmacodynamics of BAY 94-8862 and pharmacokinetics (PK) of BAY 94-8862 and three metabolites
- The influence of multiple oral doses of BAY 94-8862 given as 20 mg bid over 10 days on the PK of a single oral dose of the CYP3A4 substrate midazolam in 9 healthy male subjects.
Secondary objectives: To assess
- The pharmacodynamics of BAY 94-8862 and pharmacokinetics (PK) of BAY 94-8862 and three metabolites
- The influence of multiple oral doses of BAY 94-8862 given as 20 mg bid over 10 days on the PK of a single oral dose of the CYP3A4 substrate midazolam in 9 healthy male subjects.
Key Participants Requirements
Sex
MaleAge
18 - 45 YearsTrial summary
Enrollment Goal
47Trial Dates
August 2010 - December 2010Phase
Phase 1Could I Receive a placebo
NoProducts
Finerenone (BAY94-8862)Accepts Healthy Volunteer
YesWhere to participate
Status | Institution | Location |
---|---|---|
Completed | Wuppertal, 42096, Germany |
Primary Outcome
- Cmax (Maximum drug concentration in plasma after single dose administration for BAY 94-8862 and its metabolites for Part A and midazolam and its metabolite for Part B)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d. For midazolam on day -1d, 1d and 9d at pre dose and up to 15 h post dose.enhanced_encryptionNoSafety Issue:
- Cmax/D (Maximum drug concentration in plasma after single dose administration divided by dose for BAY 94-8862 and its metabolites in Part A on 0d)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- AUC (Area under the plasma concentration vs time curve from zero to infinity after single (first) dose for BAY 94-8862 and its metabolites for Part A and midazolam and its metabolite for Part B)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d. For midazolam on day -1d, 1d and 9d at pre dose and up to 15 h post dose.enhanced_encryptionNoSafety Issue:
- AUC/D (AUC divided by dose for BAY 94-8862 and its metabolites in Part A on 0d)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- AUCτ,md (AUC for the actual dosing interval after multiple dose administration for BAY 94-8862 and its metabolites for Part A on 9d and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- AUCτ,md/D (AUCτ,md divided by dose for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Cmax,md (Maximum drug concentration in plasma after multiple dose administration for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Cmax,md/D (Cmax,md divided by dose for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Number of participants with adverse eventsdate_rangeTime Frame:Approximately 5 weeks per subjectenhanced_encryptionYesSafety Issue:
Secondary Outcome
- AUC(0-tlast) (AUC from time 0 to the last data point for BAY 94-8862 and its metabolites for Part A on 0d and midazolam and its metabolite for Part B)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d. For midazolam on day -1d, 1d and 9d at pre dose and up to 15 h post-doseenhanced_encryptionNoSafety Issue:
- AUC(0-tlast)/D (AUC(0-tlast) divided by dose for BAY 94-8862 and its metabolites in Part A on 0d)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- AUCnorm (Area under the curve divided by dose per kg body weight after single (first) dose for BAY 94-8862 and its metabolites in Part A)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- Cmax,norm (Maximum drug concentration in plasma after single dose administration divided by dose (mg) per kg body weight for BAY 94-8862 and its metabolites in Part A)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- t½ (Half-life associated with the terminal slope for both study days for BAY 94-8862 and its metabolites for Part A on 0d and 9d and only for BAY 94-8862 and midazolam and its metabolite for Part B)date_rangeTime Frame:For Part A, (dose steps 1 and 2) up to 12 h post-dose on 0d; dose step 3, up to 15 h post-dose on 0d; up to 48 h post-dose on 9d in 3 dose steps. In Part B, for BAY 94-8862 on 9d, up to 48 h post-dose. Midazolam up to 15 h post-dose.enhanced_encryptionNoSafety Issue:
- tmax (Time to reach maximum drug concentration in plasma after both study days for BAY 94-8862 and its metabolites for Part A on 0d and 9d and only for BAY 94-8862 and midazolam and its metabolite for Part B)date_rangeTime Frame:For Part A, (dose steps 1 and 2) up to 12 h post-dose on 0d; dose step 3, up to 15 h post-dose on 0d; up to 48 h post-dose on 9d in 3 dose steps. In Part B, for BAY 94-8862 on 9d, up to 48 h post-dose. Midazolam up to 15 h post-dose.enhanced_encryptionNoSafety Issue:
- MRT (Mean residence time for both study days for BAY 94-8862 and its metabolites for Part A on 0d and 9d and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A, (dose steps 1 and 2) up to 12 h post-dose on 0d; dose step 3, up to 15 h post-dose on 0d; up to 48 h post-dose on 9d in 3 dose steps. In Part B, for BAY 94-8862 on 9d, up to 48 h post-dose.enhanced_encryptionNoSafety Issue:
- CL/f (Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance) for BAY 94-8862 and its metabolites in Part A on 0d)date_rangeTime Frame:For Part A, in dose steps 1 and 2, for BAY 94-8862 pre-dose (morning) and up to 12 h post-dose on 0d. For dose step 3, pre-dose and up to 15 h post-dose on 0d.enhanced_encryptionNoSafety Issue:
- AUCτ,md,norm (AUCτ,md divided per kg body weight for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:For Part A pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Cmax,md,norm (Cmax,md divided by dose (mg) per kg body weight for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- PTF (Peak trough fluctuation calculated as Cmax,md - Cmin/Cav with Cav =AUCτ/τ for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Cτ/Cmax (Observed concentration at the end of the dosing interval divided by maximum observed drug concentration for BAY 94-8862 and its metabolites for Part A and only for BAY 94-8862 for Part B)date_rangeTime Frame:For Part A and Part B pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- RACmax (Accumulation ratio = Cmax,md divided by Cmax for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:For Part A pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- RLin (Accumulation ratio = AUCτ,md divided by AUC for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:For Part A pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- RAAUC (Accumulation ratio = AUCτ,md divided by AUCτ on Day 0 for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:For Part A pre-dose (morning) and up to 48 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Aeur(0-24) (Amount excreted into urine from 0 to 24 h (od regimen) for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:Pre-dose and up to 24 h post-dose on 9denhanced_encryptionNoSafety Issue:
- Aeur(0-12) (Amount excreted into urine from 0 to 12 h (bid regimen) for BAY 94-8862 and its metabolites in Part A on 9d)date_rangeTime Frame:Pre-dose and up to 12 h post-dose on 9denhanced_encryptionNoSafety Issue:
- CLR (Renal body clearance of drug for BAY 94-8862 and its metabolites on day 9d in Part A)date_rangeTime Frame:Pre-dose to 12 h post-dose in bid doses and up to 24 post-dose in od dosingenhanced_encryptionNoSafety Issue:
- Cτ,md,norm (Cτ,md divided by dose (mg) per kg body weight for BAY 94-8862 in Part B only)date_rangeTime Frame:Pre-dose and up to 48 h post-doseenhanced_encryptionNoSafety Issue:
- AUC-ratio (α-hydroxymidazolam / midazolam)date_rangeTime Frame:On Day -1, Day 2 and Day 10enhanced_encryptionNoSafety Issue:
- HR over 1 minHeart rate over 1 mindate_rangeTime Frame:From 24 h prior to dosing and up to 4 post-dose on 0d. On 9d, pre-dose and up to 48 h post-dose. In between 1d and 8d at 00 h.enhanced_encryptionYesSafety Issue:
- HR (Heart rate)date_rangeTime Frame:Approximately 5 weeks per subjectenhanced_encryptionYesSafety Issue:
- BP (Blood pressure)date_rangeTime Frame:Approximately 5 weeks per subjectenhanced_encryptionYesSafety Issue:
- Neurohormones (Plasma renin activity, plasma angiotensin II, serum aldosterone and plasma noradrenaline)date_rangeTime Frame:At -1d, pre-dose on 0d, 9d, and 11denhanced_encryptionNoSafety Issue:
- Urinary electrolytes (Sodium (Na), potassium (K), magnesium)date_rangeTime Frame:From 24 h prior to dosing and up to 24 h post-dose on both the profile days, 0d and 9d and additionally single samples were collected at 00 h from 2d to 7denhanced_encryptionYesSafety Issue:
- Urinary creatininedate_rangeTime Frame:From 24 h prior to dosing and up to 24 h post dose on both the profile days, 0d and 9d and additionally single samples were collected at 00 h from 2d to 7denhanced_encryptionYesSafety Issue:
- Urinary volumedate_rangeTime Frame:From 24 h prior to dosing and up to 24 h post-dose on both the profile days, 0d and 9d and additionally single samples were collected at 00 h from 2d to 7denhanced_encryptionYesSafety Issue:
- PTF (Peak trough fluctuation calculated as Cmax,md Cmin/Cav with Cav =AUCτ/τ for BAY 94-8862 and its metabolites for Part A on 9d and for BAY 94-8862 in Part B)date_rangeTime Frame:Pre-dose and up to 48 h post-dose in both Part A and B on 9denhanced_encryptionNoSafety Issue:
- Ctrough (For BAY 94-8862 and its metabolites in Part A, and BAY 94-8862 in Part B)date_rangeTime Frame:Between 0d and 9d in both Part A and Benhanced_encryptionNoSafety Issue:
Trial design
Trial Type
InterventionalIntervention Type
DrugTrial Purpose
OtherAllocation
RandomizedBlinding
Single BlindAssignment
Parallel AssignmentTrial Arms
3