Pharmacokinetics in Subjects With Renal Impairment

NCT ID: NCT01504165

Last Updated: 2014-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2012-04-30

Brief Summary

This is an open-label, non-randomized, parallel-group, mono-center, single intravenous dose, Phase I trial to investigate the Pharmacokinetic (PK) and safety of cilengitide in subjects with different grades of renal impairment as compared to subjects with normal renal function.

Detailed Description

Subjects with impaired renal function will be screened and will be stratified by their estimated glomerular filtration rate (GFR) according to the Modification of Diet in Renal Disease (MDRD) equation and assigned to one of the stratification groups defined below:

Group Number/Renal function/Creatinine Clearance (GFR according to MDRD)

1. Normal renal function (≥ 90 mL/min)

2. Mild renal impairment (60 - 89 mL/min)

3. Moderate renal impairment (30 - 59 mL/ min) 4a: Severe renal impairment (< 30 mL/min) - no dialysis required 4b: (if applicable) Severe renal impairment (< 30 mL/min) - no dialysis required

Subjects in Groups 2 and 3 will receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion. Subjects from group 4a will receive a single dose of 1000mg of cilengitide as 1-hour i.v. infusion . PK samples will be collected and basic PK parameters will be calculated. The safety, tolerability, and PK will be evaluated by the Safety Monitoring Committee (SMC). If the SMC has no concerns, Group 4b will be treated with a higher dose (up to 2000mg) of cilengitide. Then, Group 1 (healthy subjects) will be started after the last subject with renal impairment (in either Group 2, 3, or 4a; or in Group 4b, if applicable) has completed all activities on Day 3. They will also receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion.

The duration of the trial from the first subject enrolled to the last subject last visit will be approximately 6 months (approximately 8 months, in case Group 4b is included). Each subject will participate in the trial for up to 35 days, including screening and the end of trial examination.

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

Group 1

Healthy volunteers: matched subjects with normal renal function

Group Type: EXPERIMENTAL

cilengitide 2000mg

Intervention Type: DRUG

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Group 2

Mild renal impaired subjects

Group Type: EXPERIMENTAL

cilengitide 2000mg

Intervention Type: DRUG

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Group 3

Moderate renal impaired subjects

Group Type: EXPERIMENTAL

cilengitide 2000mg

Intervention Type: DRUG

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Group 4a

First group of Severe renal impaired subjects

Group Type: EXPERIMENTAL

cilengitide 1000mg

Intervention Type: DRUG

A single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1

Group 4b

Second group of severe renal impaired subjects

Group Type: EXPERIMENTAL

cilengitide > 1000mg and up to 2000mg

Intervention Type: DRUG

A single dose of cilengitide \> 1000mg and up to 2000mg will be administered as 1-hour i.v. infusion on Day 1 if applicable, based on Safety Monitoring Committee decision

Interventions

cilengitide 2000mg

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Intervention Type: DRUG

cilengitide 2000mg

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Intervention Type: DRUG

cilengitide 2000mg

A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1

Intervention Type: DRUG

cilengitide 1000mg

A single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1

Intervention Type: DRUG

cilengitide > 1000mg and up to 2000mg

A single dose of cilengitide \> 1000mg and up to 2000mg will be administered as 1-hour i.v. infusion on Day 1 if applicable, based on Safety Monitoring Committee decision

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI): ≥ 18 kg/m² and ≤ 35 kg/m²

For subjects with normal renal function:

• Vital signs (pulse rate and blood pressure) within the normal range or showing no clinically relevant deviation
• Estimated creatinine clearance according to the MDRD equation of ≥ 90 mL/min at Screening

For subjects with impaired renal function:

• Laboratory parameters should be within acceptable range for subjects with renal impairment,
• Vital signs: Pulse rate within the normal range of 45-100 beats/minute in supine position after 5 minutes of rest. Blood pressure diastolic below 100 mmHg, and systolic below 160 mmHg for Groups 1-3 and below 180 mmHg for Group 4a and 4b, in supine position after 5 minutes of rest
• Calculated creatinine clearance according to the MDRD equation of < 90 mL/min at Screening and the possibility of stratification to one of the Groups.

Exclusion Criteria

• History of malignant disease within the last 5 years or acute malignant disease
• Medical history of wound healing problems and/or any current open wounds
• Current or history of bleeding disorders and/or history of thromboembolic events (considering family history as well); thrombolytics or oral or parenteral anticoagulants within 30 days prior to Day 1
• Electrocardiogram recording (12-lead ECG) with signs of clinically relevant pathology as judged by the Investigator

For subjects with impaired renal function:

• Chronic heart failure non stabilized (New York Heart Association [NYHA] class III and IV)
• Acute renal failure of any etiology (including viral, toxic, or drug induced)
• Requiring dialysis
• History of renal transplantation
• Uncontrolled diabetes mellitus as judged by the Investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Becker, MD MSc

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

For Research Sites contact Merck KGaA Communication Center in

Darmstadt, , Germany

CRS Clincial Research Services Kiel GmbH

Kiel, , Germany

Countries

Germany

Other Identifiers

2011-002389-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR062041_016

Identifier Type: -

Identifier Source: org_study_id