Phase 1
Completed N=12
Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT03796182 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Feb 2020
Primary outcomePrimary: Renal Clearance (CLr) of Metformin — 32.18; 33.33 litre per hour (L/hr)
Summary
This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842 on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its correlation to the effect on metformin PK will also be assessed. Participants will be randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male and/or female participants will be enrolled in the study so that 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Renal Clearance (CLr) of Metformin |
32.18; 33.33 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin |
5050; 5202 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Metformin |
634.7; 720.7 | — |
| SECONDARY Time for Cmax (Tmax) of Metformin |
4.00; 4.00 | — |
| SECONDARY Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin |
4849; 5145 | — |
| SECONDARY Apparent Clearance (CL/F) of Metformin |
98.97; 96.13 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Metformin |
1087; 1211 | — |
| SECONDARY Terminal Half-life (t1/2) of Metformin |
8.318; 9.261 | — |
| SECONDARY Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin |
168.0; 170.5 | — |
| SECONDARY Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin |
33.60; 34.05 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities |
0; 0 | — |
| SECONDARY Number of Participants With Categorical Vital Signs Meeting Pre-defined Criteria |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related) |
6; 4; 5; 4; 0; 0 | — |
| SECONDARY Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related) |
50.0; 33.3; 41.7; 33.3; 0.0; 0.0 | — |
Eligibility Criteria
Inclusion Criteria
- Male and female participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and cardiovascular tests.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- Female participants who are of child bearing potential must not be intending to become pregnant, currently pregnant, or lactating.
- Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
- Capable of giving signed informed consent.
Exclusion Criteria
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
- Any condition possibly affecting drug absorption (eg, gastrectomy).
- History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C virus antibody (HCVAb).
- Other acute or chronic medical or psychiatric condition including recent (within the past year).
- Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) or visible rash present during physical examination.
- Clinically relevant history of lactic acidosis.
- Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product.
- A positive urine drug test.
- Selected laboratory abnormalities.
- History of regular alcohol consumption exceeding 14 drinks/week for female participants or 21 drinks/week for male participants (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
- Known relevant history of elevated liver function tests (LFTs).
- History of tuberculosis (TB) (active or latent)
- Any history of chronic infections, any history of recurrent infections, any history of latent infections, or any acute infection within 2 weeks of baseline.
- History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
Data sourced from ClinicalTrials.gov (NCT03796182). 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.