Phase 1
Completed N=66
A Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06700841, With Bioavailability/Food Effect Investigation
Source: ClinicalTrials.gov NCT02310750 ↗Enrolled (actual)
66
Serious AEs
0.0%
Results posted
Mar 2017
Primary outcomePrimary: Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1 — 114.2; 110.6; 108.7; 102.8 millimeter of mercury (mmHg)
Summary
The main purpose of the study is to determine if PF-06700841 is safe and well tolerated when administered to humans. A secondary purpose is to assess what the body does to PF-06700841 and to assess what PF-06700841 does to the body when given as single and multiple doses. The pharmacokinetic properties of different forms of PF-06700841 may be studied (tablet and solution/suspension forms).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1 |
114.2; 110.6; 108.7; 102.8; 117.8; 112.4 | — |
| PRIMARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Blood Pressure at Day 10 |
112.2; 106.5; 103.6; 110.3; 111.5; 108.6 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Blood Pressure at Day 28 |
115.0; 120.1; 112.9; -5.3; -8.9; 1.0 | — |
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Pulse Rate at Day 1 |
57.5; 68.6; 67.2; 56.0; 67.3; 55.8 | — |
| PRIMARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Pulse Rate at Day 10 |
59.3; 59.0; 55.8; 60.8; 61.5; 66.0 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Pulse Rate at Day 28 |
61.8; 61.4; 64.9; -1.9; -5.3; -3.0 | — |
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Oral Temperature at Day 1 |
36.79; 36.83; 36.65; 36.82; 36.80; 36.69 | — |
| PRIMARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Oral Temperature at Day 10 |
36.71; 36.70; 36.76; 36.68; 36.83; 36.76 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Oral Temperature at Day 28 |
36.74; 36.67; 36.80; 0.01; -0.04; -0.20 | — |
| PRIMARY Number of Participants With Change From Baseline in Physical Examinations |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 1 |
175.7; 149.7; 163.1; 168.2; 163.6; 175.8 | — |
| PRIMARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 10 |
176.9; 180.0; 167.6; 169.0; 168.5; 171.6 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 28 |
169.4; 156.1; 154.7; -0.6; 11.1; 4.1 | — |
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Heart Rate at Day 1 |
56.1; 70.3; 69.2; 55.3; 67.7; 53.0 | — |
| PRIMARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Heart Rate at Day 10 |
55.1; 55.5; 55.4; 61.0; 58.5; 63.0 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Heart Rate at Day 28 |
63.1; 60.2; 66.0; 5.2; 4.0; 1.4 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation Due to AEs |
2; 1; 1; 0; 1; 3 | — |
| PRIMARY Number of Adverse Events (AEs) According to Severity |
2; 1; 1; 0; 1; 4 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities |
7; 4; 4; 6; 6; 6 | — |
| PRIMARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Creatinine Clearance at Day 1 |
117.7; 93.0; 133.8; 95.8; 117.0; 129.6 | — |
| PRIMARY Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 10 |
114.4; 111.0; 112.6; 115.0; 142.5; 138.4 | — |
| PRIMARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 28 |
-10.0; -35.0; -67.6 | — |
| PRIMARY Food Effect Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841 |
6463; 6720; 5321 | — |
| PRIMARY Food Effect Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841 |
6447; 6694; 5305 | — |
| PRIMARY Food Effect Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841 |
1022; 1084; 656.6 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841 |
5.138; 18.21; 79.30; 271.3; 748.4; 2460 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06700841 |
1.00; 1.00; 0.500; 1.00; 1.00; 1.00 | — |
| SECONDARY Food Effect Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF--06700841 |
0.500; 1.00; 4.00 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841 |
NA; 145.8; 353.8; 1439; 4797; 18410 | — |
| SECONDARY Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06700841 |
422.8; 1880; 6089; 3560; 16180; 990.0 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841 |
17.71; 79.18; 340.4; 1431; 5041; 18400 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06700841 |
5.138; 6.061; 7.930; 9.033; 7.484; 12.31 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf[dn]) of PF-06700841 |
NA; 48.65; 35.38; 47.97; 47.97; 92.13 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06700841 |
17.71; 26.38; 34.04; 47.64; 50.41; 92.09 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau[dn]) of PF-06700841 |
42.28; 62.68; 60.89; 71.15; 92.30 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Plasma Decay Half-Life (t1/2) of PF-06700841 |
NA; 4.554; 3.848; 4.363; 7.519; 6.813 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Mean Residence Time (MRT) of PF-06700841 |
NA; 6.414; 5.169; 5.206; 7.277; 8.758 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Volume of Distribution (Vz/F) of PF-06700841 |
NA; 126.4; 151.0; 115.7; 210.5; 102.4 | — |
| SECONDARY Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Clearance (CL/F) of PF-06700841 |
NA; 20.57; 28.26; 20.82; 20.85; 10.86 | — |
| SECONDARY Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Peak-Trough Fluctuation (PTF) of PF-06700841 |
2.815; 3.543; 2.643; 1.297; 2.911; 3.414 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Amount of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau) |
1.109; 2.798; NA; 7.758; 15.60 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Percentage of Dose of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau%) |
11.09; 9.332; NA; 15.54; 8.910 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Renal Clearance |
2.619; 1.486; NA; 2.179; 0.9629 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Baseline |
119.17; 188.76; 219.62; 78.28; 141.38; 115.00 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 10, 11, 28 |
114.04; 85.50; 101.12; 142.23; 106.43; 121.60 | — |
| SECONDARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Interferon Gamma-Induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 7, 14, 21, 28, 29, 35, 56 |
302.00; 127.58; 123.09; 53.44; -8.51; -49.57 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: High Sensitivity C-reactive Protein (hsCRP) Concentration in Serum at Baseline |
0.1220; 0.1066; 0.6420; 0.0757; 0.2290; 0.1158 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 10, 11, 28 |
0.0974; 0.0815; 0.1002; 0.0983; 0.0505; 0.0746 | — |
| SECONDARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 7, 14, 21, 28, 29, 35 and 56 |
1.0699; 0.5694; 0.3143; -0.1096; -0.3408; -0.0189 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Neutrophil Counts at Day 2, 5 and 8 |
2.988; 2.433; 3.097; 2.500; 3.048; 2.973 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Neutrophil Counts at Day 4, 8, 10, 11, 14, 28 |
2.584; 2.340; 2.676; 2.770; 2.710; 2.690 | — |
| SECONDARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Neutrophil Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56 |
4.109; 3.640; 3.909; -0.402; 0.006; 0.153 | — |
| SECONDARY Single Ascending Dose (SAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 2, 5, 8 |
1.23; 1.19; 0.98; 1.25; 1.25; 1.44 | — |
| SECONDARY Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 8, 10, 11, 14 and 28 |
1.26; 0.85; 1.22; 1.03; 1.40; 2.26 | — |
| SECONDARY Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56 |
1.49; 1.45; 1.31; -0.10; -0.09; -0.13 | — |
Eligibility Criteria
Inclusion Criteria
Key Inclusion Criteria for Healthy Subject Cohorts:
- Healthy male subjects and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive
- No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
Key Inclusion Criteria for Psoriasis Subject Cohorts:
- Male subjects and/or female subjects of non-childbearing potential with a diagnosis of plaque psoriasis who are between the ages of 18 and 65 years, inclusive
- Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
Exclusion Criteria
Key Exclusion Criteria for Healthy Subject Cohorts:
- 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)
- Males of childbearing potential 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
Key Exclusion Criteria for Psoriasis Subject Cohorts:
- Currently have non plaque forms of psoriasis, (eg, erythrodermic, guttate, or pustular psoriasis).
- Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium
- Males of childbearing potential 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 (NCT02310750). 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.