Phase 1
Completed N=109
A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis
Source: ClinicalTrials.gov NCT03210961 ↗Enrolled (actual)
109
Serious AEs
0.0%
Results posted
Mar 2020
Primary outcomePrimary: Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period) — 2; 2; 1; 0 Participants
Summary
This first in human study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06826647 in healthy subjects and subjects with plaque psoriasis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Single Ascending Dose [SAD] Period) |
2; 2; 1; 0; 1; 0 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Multiple Ascending Dose [MAD] Period) |
1; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) |
0; 1; 1; 0; 3; 5 | — |
| PRIMARY Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (SAD Period) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (MAD Period) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Physical Examination Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria (SAD Period) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With ECG Data Meeting Pre-Specified Criteria (MAD Period) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With ECG Data Meeting Pre-Specified Criteria (Psoriasis Cohorts) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Who Withdrew Due to Adverse Events (AEs) (SAD Period) |
1; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (MAD Period) |
2; 0; 2; 1; 1; 1 | — |
| PRIMARY Number of Participants With TEAEs, SAEs, and Who Withdrew Due to AEs (Psoriasis Cohorts) |
7; 12; 5; 5; 5; 3 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities (SAD Period) |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities (MAD Period) |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities (Psoriasis Cohorts) |
2; 3; 1; 1; 1; 0 | — |
| PRIMARY Change in 24 Hour Creatinine Clearance From Day -1 on Day 10 (MAD Period) |
-21.0; -32.0; -62.4; 0.2; -52.5; -11.4 | — |
| SECONDARY Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) (SAD Period) |
47.63; 369.3; 848.4; 1582; 3056; 11790 | — |
| SECONDARY Secondary: Dose Normalized AUCinf (AUCinf[dn]) (SAD Period) |
15.86; 36.93; 28.28; 15.82; 7.636; 7.370 | — |
| SECONDARY Area Under the Concentration-Time Profile From Time 0 to 24 Hours (AUC24) (SAD Period) |
43.10; 347.8; 543.2; 1158; 2519; 9318 | — |
| SECONDARY Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) (SAD Period) |
40.25; 354.8; 638.5; 1375; 2767; 9921 | — |
| SECONDARY Dose Normalized AUClast (AUClast[dn]) (SAD Period) |
13.40; 35.48; 21.28; 13.75; 6.919; 6.200 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) (SAD Period) |
7.844; 47.09; 77.93; 166.8; 404.8; 1218 | — |
| SECONDARY Dose Normalized Cmax (Cmax[dn]) (SAD Period) |
2.617; 4.709; 2.597; 1.668; 1.012; 0.7618 | — |
| SECONDARY Time for Cmax (Tmax) (SAD Period) |
2.00; 2.00; 2.00; 2.00; 2.00; 2.00 | — |
| SECONDARY Terminal Elimination Half-Life ((t½) (SAD Period) |
3.620; 6.032; 19.69; 38.77; 16.25; 22.21 | — |
| SECONDARY Mean Residence Time (MRT) (SAD Period) |
5.596; 7.761; 16.97; 21.23; 10.56; 9.417 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) (SAD Period) |
312.1; 226.1; 902.9; 2671; 2732; 2877 | — |
| SECONDARY Apparent Clearance (CL/F) (SAD Period) |
62.98; 27.08; 35.36; 63.21; 130.8; 135.4 | — |
| SECONDARY Area Under the Plasma Concentration-Time Profile Over the Dosing Interval τ (AUCτ) (MAD Period Day 1) |
662.8; 1803; 1646; 4424; 6038; 17090 | — |
| SECONDARY Dose Normalized AUCτ (AUCτ[dn]) (MAD Period Day 1) |
22.10; 18.03; 8.229; 11.07; 15.10; 14.23 | — |
| SECONDARY Cmax (MAD Period Day 1) |
83.53; 267.2; 289.8; 585.9; 695.5; 2023 | — |
| SECONDARY Cmax(dn) (MAD Period Day 1) |
2.787; 2.672; 1.450; 1.468; 1.741; 1.686 | — |
| SECONDARY Tmax (MAD Period Day 1) |
3.00; 4.00; 4.00; 3.00; 4.00; 2.00 | — |
| SECONDARY AUCτ (MAD Period Day 10) |
752.9; 1952; 2010; 5420; 7194; 14890 | — |
| SECONDARY AUCτ(dn) (MAD Period Day 10) |
25.06; 19.52; 10.04; 13.56; 18.00; 12.41 | — |
| SECONDARY Cmax (MAD Period Day 10) |
85.34; 263.2; 339.5; 667.3; 887.0; 1855 | — |
| SECONDARY Cmax(dn) (MAD Period Day 10) |
2.844; 2.632; 1.701; 1.669; 2.220; 1.547 | — |
| SECONDARY Tmax (MAD Period Day 10) |
4.00; 4.00; 4.00; 4.00; 4.00; 4.00 | — |
| SECONDARY Average Concentration at Steady State (Cav) (MAD Period Day 10) |
31.36; 81.28; 167.6; 226.0; 299.7; 619.9 | — |
| SECONDARY Lowest Concentration Observed During the Dosing Interval τ (Cmin) (MAD Period Day 10) |
6.273; 10.40; 55.01; 24.77; 29.50; 62.26 | — |
| SECONDARY Terminal Elimination Half-Life ((t½) (MAD Period Day 10) |
8.802; 12.72; 26.93; 7.500; 7.433; 34.33 | — |
| SECONDARY MRT (MAD Period Day 10) |
10.56; 9.872; 17.14; 9.622; 7.996; 9.165 | — |
| SECONDARY Peak Trough Ratio (PTR) (MAD Period Day 10) |
13.61; 25.31; 6.951; 26.92; 30.09; 29.76 | — |
| SECONDARY Observed Accumulation Ratio Based on AUC (Rac) (MAD Period Day 10) |
1.085; 1.082; 1.328; 1.225; 1.191; 0.8711 | — |
| SECONDARY Observed Accumulation Ratio Based on Cmax (Rac,Cmax) (MAD Period Day 10) |
0.9295; 0.9852; 1.282; 1.139; 1.275; 0.9176 | — |
| SECONDARY Vz/F (MAD Period Day 10) |
433.5; 643.6; 3224; 758.9; 519.2; 2944 | — |
| SECONDARY CL/F (MAD Period Day 10) |
39.86; 51.27; 99.47; 73.78; 55.62; 80.63 | — |
| SECONDARY Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ) (MAD Period Day 10) |
0.2204; 1.072; 2.560; 3.134; 2.931; 14.73 | — |
| SECONDARY Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τ Hours Post-Dose (Aeτ%) (MAD Period Day 10) |
0.7344; 1.072; 1.280; 0.7827; 0.7333; 1.228 | — |
| SECONDARY Renal Clearance (Clr) (MAD Period Day 10) |
0.2928; 0.5500; 1.274; 0.5777; 0.4076; 0.9909 | — |
| SECONDARY AUCτ (Psoriasis Cohorts) |
2401; 7664 | — |
| SECONDARY AUCτ(dn) (Psoriasis Cohorts) |
24.01; 19.17 | — |
| SECONDARY Cmax (Psoriasis Cohorts) |
296.6; 869.8 | — |
| SECONDARY Cmax(dn) (Psoriasis Cohorts) |
2.966; 2.176 | — |
| SECONDARY Tmax (Psoriasis Cohorts) |
4.00; 4.00 | — |
| SECONDARY Cav (Psoriasis Cohorts) |
100.2; 319.3 | — |
| SECONDARY Cmin (Psoriasis Cohorts) |
21.92; 38.12 | — |
| SECONDARY Terminal Elimination Half-Life ((t½) (Psoriasis Cohorts) |
7.796; 6.809 | — |
| SECONDARY MRT (Psoriasis Cohorts) |
11.27; 9.444 | — |
| SECONDARY PTR (Psoriasis Cohorts) |
13.52; 22.81 | — |
| SECONDARY Vz/F (Psoriasis Cohorts) |
408.1; 461.2 | — |
| SECONDARY CL/F (Psoriasis Cohorts) |
41.61; 52.21 | — |
| SECONDARY Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 28 |
-11.13; -24.18; -14.62 | — |
Eligibility Criteria
Healthy Participants:
Inclusion Criteria
- Healthy male subjects between ages of 18-55 years
- Healthy female subjects of non-childbearing potential between the ages of 18-55 years
- Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight >50kg (110lbs).
- No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
- (Optional) Japanese subjects who have four Japanese biologic grandparents born in Japan
Exclusion Criteria
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
- Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
- Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product
- Have a clinically significant infection currently or within 6 months of first dose of study drug
Psoriasis Participants:
Inclusion Criteria
- Healthy male subjects between ages of 18-65 years
- Healthy female subjects of non-childbearing potential between the ages of 18-65 years
- Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
- Have plaque-type psoriasis covering at least 15% of total body surface area (BSA) at Day-1(prior to randomization in the study
- No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
Exclusion Criteria
- Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis
- Have a clinically significant infection currently or within 6 months of first dose of study drug, or a history of chronic or recurrent infectious disease
- Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
- Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product
Data sourced from ClinicalTrials.gov (NCT03210961). 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.