Pharmacokinetics in Subjects With Renal Impairment

NCT01504165 | Completed Phase 1

• 2 other identifiers: EMR062041_0162011-002389-19
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Impairment

Keywords

Renal impairment; Pharmacokinetic; cilengitide; subjects with mild; moderate or severe renal impairment compared to subjects with normal renal function

Outcome Measures

Primary Outcomes (2)

• Peak Plasma Concentration (Cmax) of cilengitide in plasma

  Cmax of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.

  48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

• Area under the plasma concentration versus time curve (AUC) of cilengitide in plasma

  AUC of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.

  48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

Secondary Outcomes (6)

• Terminal half life t1/2 of cilengitide

  48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

• Plasma clearance of cilengitide (CL)

  48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

• Cilengitide volume of distribution (Vz) in plasma

  48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

• Absolute and relative amount of cilengitide excreted into urine (Ae0-∞)

  24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

• Renal clearance of cilengitide (CLR)

  24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion

Study Arms (5)

Group 1

EXPERIMENTAL

Healthy volunteers: matched subjects with normal renal function

Drug: cilengitide 2000mg

Group 2

EXPERIMENTAL

Mild renal impaired subjects

Drug: cilengitide 2000mg

Group 3

EXPERIMENTAL

Moderate renal impaired subjects

Drug: cilengitide 2000mg

Group 4a

EXPERIMENTAL

First group of Severe renal impaired subjects

Drug: cilengitide 1000mg

Group 4b

EXPERIMENTAL

Second group of severe renal impaired subjects

Drug: cilengitide > 1000mg and up to 2000mg

Interventions

cilengitide 2000mg DRUG

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

Group 1

cilengitide 1000mg DRUG

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

Group 4a

cilengitide > 1000mg and up to 2000mg 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

Group 4b

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (2)

For Research Sites contact Merck KGaA Communication Center in

Darmstadt, Germany

Location

CRS Clincial Research Services Kiel GmbH

Kiel, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency; Lymphoma, Follicular

Interventions

Cilengitide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Andreas Becker, MD MSc

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2012
• First Posted: January 5, 2012
• Study Start: January 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: February 4, 2014

Record last verified: 2014-02

Locations

DE (2)