Phase 1
Completed N=29
A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function
Source: ClinicalTrials.gov NCT00759564 ↗Enrolled (actual)
29
Serious AEs
1.8%
Results posted
Jan 2016
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose — 17700; 22070; 28940; 10340 nanogram per milliliter (ng/mL)
Summary
This study will evaluate what effect renal dysfunction has on a drug that has an intravenous (CP-70,429) and an oral form (PF-03709270).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose |
17700; 22070; 28940; 10340 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following CP-70,429 Intravenous Dose |
1.00; 1.50; 1.50; 1.50 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following CP-70,429 Intravenous Dose |
31990; 53610; 78940; 34270 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70,429 Following CP-70,429 Intravenous Dose |
32160; 54070; 79870; 35410 | — |
| PRIMARY Renal Clearance (CLr) of CP-70429 Following CP-70,429 Intravenous Dose |
8.035; 6.936; 3.043; 2.303 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following PF-03709270 Oral Dose |
2747; 3704; 6215; 7830 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-70429 Following PF-03709270 Oral Dose |
1.50; 2.50; 1.50; 2.50 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-70429 Following PF-03709270 Oral Dose |
6403; 13400; 22600; 47560 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of CP-70429 Following PF-03709270 Oral Dose |
6523; 13670; 23040; 47990 | — |
| PRIMARY Renal Clearance (CLr) of CP-70429 Following PF-03709270 Oral Dose |
15.47; 7.952; 4.239; 3.294 | — |
| SECONDARY Terminal Elimination Half Life (t1/2) of CP-70429 Following CP-70,429 Intravenous Dose |
1.034; 1.660; 1.823; 2.313 | — |
| SECONDARY Terminal Elimination Half Life (t1/2) of CP-70429 Following PF-03709270 Oral Dose |
0.837; 1.451; 1.809; 2.750 | — |
| SECONDARY Clearance (CL) |
24.87; 14.79; 10.01; 5.648 | — |
| SECONDARY Apparent Oral Clearance (CL/F) |
153.5; 73.20; 43.38; 20.86 | — |
| SECONDARY Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following Intravenous Dose |
5.310; 8.855; 11.40; 10.70 | — |
| SECONDARY Duration of Plasma Concentrations of CP-70429 Exceeding 0.5 Microgram Per Milliliter Following PF-03709270 Oral Dose |
3.915; 6.440; 8.185; 18.30 | — |
| SECONDARY Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following Intravenous Dose |
3.935; 7.190; 9.240; 7.710 | — |
| SECONDARY Duration of Plasma Concentrations of CP-70429 Exceeding 1.0 Microgram Per Milliliter Following PF-03709270 Oral Dose |
2.895; 4.990; 6.320; 12.15 | — |
| SECONDARY Pharmacokinetics of CP-70429 and PF-03709270 Metabolites |
— | — |
| SECONDARY Concentration Versus Time Summary of 2-Ethylbutyric Acid |
46.38; 19.00; 15.25; NA; 20.00; 17.63 | — |
| SECONDARY Concentration Versus Time Summary of Plasma Formate |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
5; 5; 4; 0; 3; 6 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities |
2; 3; 7; 1; 4; 1 | — |
| SECONDARY Number of Participants With Vital Sign Abnormalities |
0; 0; 1; 0; 1; 0 | — |
| SECONDARY Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 3; 0; 0; 3; 1 | — |
| SECONDARY Number of Participants With Change From Baseline in Physical Examinations |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
Subjects must meet one of the following renal function categories:
- Normal renal function (CLcr >80 mL/min).
- Mild renal impairment (CLcr >50 and 30 and <50 mL/min).
- Severe renal impairment (CLcr <30 mL/min).
Exclusion Criteria
Women who are pregnant or nursing or women who are of childbearing potential. History of clinically significant allergies, including seasonal allergies, and especially drug hypersensitivity including known allergies to components of the study drug formulation, penicillin, carbapenems and/or cephalosporin antibiotics (eg, amoxicillin, amoxicillin/clavulanate, ampicillin, cefadroxil, cephalexin, cefaclor and cefixime).
Subjects should not have evidence of a history of the following:
- normal renal function: clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological or allergic disease.
- renal impairment: any clinically significant (hepatic, cardiac or pulmonary or subjects with acute nephritic syndrome) diseases (except diabetes). Stable co-morbid disease where it is unlikely that the disease and medication will alter the outcome of the study will be allowed.
Data sourced from ClinicalTrials.gov (NCT00759564). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.