Effect of Repeated Doses of BI 1060469 and BI 1021958 on Glomerular Filtration Rate (GFR) in Healthy Volunteers

Effect of Repeated Oral Doses of BI 1060469, BI 1021958 and Active Controls, Cimetidine and Naproxen, on Measured GFR Via Renal Clearance of Iohexol in Healthy Male Subjects (a Phase I Study; Single-blind, Randomized, Placebo-controlled Within BI Groups and Open-label for the Active Controls)

Main objective is to investigate the measured glomerular filtration rate (mGFR) as assessed by iohexol clearance in healthy male normovolemic subjects after oral administration of single and repeated doses of BI 1060469, and BI 1021958.

The secondary objective of this trial is to investigate the glomerular filtration rate (GFR) as assessed by 24 hours creatinine clearance in healthy male normovolemic subjects after oral administration of single and repeated doses of BI 1060469, and BI 1021958.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Naproxen; Drug: Placebo; Drug: BI 1060469 low dose; Drug: BI 1060469 high dose; Drug: Cimetidine; Drug: BI 1021958

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1333.43.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy male subjects according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests, including negative test result on occult blood in stool (only for subjects assigned to Naproxen)
• Age 18 to 45 years (incl.)
• Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
• 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 BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator
• Repeated measurement of systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or pulse rate outside the range of 50 to 90 mmHg
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Serum creatinine laboratory value out of the normal range
• GFR (Glomerular Filtration Rate) < 90 mL/ min at screening
• Urinary toral protein/creatinine ratio > 0,1 mg protein/ mg creatinine
• Current or history of relevant kidney, urinary tract diseases or abnormalities (i.e. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure, infections)
• Further exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Naproxen	Drug: Naproxen
Experimental: BI 1060469 low dose; Low-Dose,Tablet,oral administration with 240 ml water,over 10 days	Drug: Placebo; tablets; Drug: BI 1060469 low dose; tablets
Experimental: BI 1060469 high dose; High-Dose,Tablets,oral administration with 240 ml water, over 10 days	Drug: Placebo; tablets; Drug: BI 1060469 high dose; tablets
Active Comparator: Cimetidine	Drug: Cimetidine
Experimental: BI 1021958; High-Dose,Tablets,oral administration with 240 ml water, over 10 days	Drug: Placebo; tablets; Drug: BI 1021958; tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
measured glomerular filtration rate (mGFR) based on renal iohexol clearance	up to day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
measured urinary 24-hour creatinine clearance	up to day 11

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (Estimate): July 29, 2014

Study Record Updates

• Last Update Posted (Estimate): December 24, 2014
• Last Update Submitted That Met QC Criteria: December 23, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Gout Suppressants; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Naproxen; Cimetidine
• Other Study ID Numbers: 1333.43; 2014-000320-20 (EudraCT Number: EudraCT)