Pharmacokinetics in Subjects With Renal Impairment
Condition: Renal Impairment
MeSH terms: Renal Insufficiency
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): cilengitide 2000mg; cilengitide 2000mg; cilengitide 2000mg; cilengitide 1000mg; cilengitide > 1000mg and up to 2000mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1; A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1; A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1; A single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1; 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
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Renal impairment; Pharmacokinetic; cilengitide; subjects with mild; moderate or severe renal impairment compared to subjects with normal renal function