Pharmacokinetics in Subjects With Renal Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01504165
First received: January 3, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Renal Impairment
Drug: cilengitide 2000mg
Drug: cilengitide 1000mg
Drug: cilengitide > 1000mg and up to 2000mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase I, Open-label, Parallel-group, Mono-center Trial to Investigate the Pharmacokinetics of a Single Intravenous Dose of Cilengitide in Subjects With Mild, Moderate or Severe Renal Impairment Compared to Subjects With Normal Renal Function

Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Peak Plasma Concentration (Cmax) of cilengitide in plasma [ Time Frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
    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.

  • Area under the plasma concentration versus time curve (AUC) of cilengitide in plasma [ Time Frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Terminal half life t1/2 of cilengitide [ Time Frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
  • Plasma clearance of cilengitide (CL) [ Time Frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
  • Cilengitide volume of distribution (Vz) in plasma [ Time Frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
  • Absolute and relative amount of cilengitide excreted into urine (Ae0-∞) [ Time Frame: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
  • Renal clearance of cilengitide (CLR) [ Time Frame: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]
  • Plasma-protein-binding: Fraction unbound of cilengitide [ Time Frame: 2 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: January 2012
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Healthy volunteers: matched subjects with normal renal function
Drug: cilengitide 2000mg
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
Experimental: Group 2
Mild renal impaired subjects
Drug: cilengitide 2000mg
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
Experimental: Group 3
Moderate renal impaired subjects
Drug: cilengitide 2000mg
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
Experimental: Group 4a
First group of Severe renal impaired subjects
Drug: cilengitide 1000mg
A single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1
Experimental: Group 4b
Second group of severe renal impaired subjects
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504165

Locations
Germany
For Research Sites contact Merck KGaA Communication Center in
Darmstadt, Germany
CRS Clincial Research Services Kiel GmbH
Kiel, Germany
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Andreas Becker, MD MSc Merck Serono S.A., Geneva
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01504165     History of Changes
Other Study ID Numbers: EMR062041_016, 2011-002389-19
Study First Received: January 3, 2012
Last Updated: February 3, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Merck KGaA:
Renal impairment
Pharmacokinetic
cilengitide
subjects with mild
moderate or severe renal impairment compared to subjects with normal renal function

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014