4-Week, Multiple-dose, Dose-escalating Study In Patients With Type 2 Diabetes
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03538743
Collaborator
(none)
98
4
9
11.5
24.5
2.1
Study Details
Study Description
Brief Summary
This is a dose-escalating study in patients with Type 2 diabetes on metformin. Participants will receive an investigational product or placebo for 28 days.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
98 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF MULTIPLE ESCALATING ORAL DOSES OF PF-06882961 IN ADULT SUBJECTS WITH TYPE 2 DIABETES MELLITUS
Actual Study Start Date
:
Jun 25, 2018
Actual Primary Completion Date
:
May 23, 2019
Actual Study Completion Date
:
Jun 10, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: Placebo
Tablet, 0 mg, twice daily, 28 days
|
| Experimental: PF-06882961 30 mg
|
Drug: PF-06882961
Tablet, 15 mg twice daily, 28 days
|
| Experimental: PF-06882961 100 mg
|
Drug: PF-06882961
Tablet, 50 mg twice daily, 28 days
|
| Experimental: PF-06882961 300 mg
|
Drug: PF-06882961
Tablet, 150 mg twice daily, 28 days
|
| Experimental: PF-06882961 600 mg
|
Drug: PF-06882961
Tablet, 300 mg twice daily, 28 days
|
| Experimental: PF-06882961 dose TBD Cohort 5
|
Drug: PF-06882961
Tablet, dose TBD, twice daily, Cohort 5, 28 days
|
| Experimental: PF-06882961 dose TBD Cohort 6
|
Drug: PF-06882961
Tablet, dose TBD, twice daily, Cohort 6, 28 days
|
| Experimental: PF-06882961 dose TBD Cohort 7
|
Drug: PF-06882961
Tablet, dose TBD, twice daily, Cohort 7, 28 days
|
| Experimental: PF-06882961 dose TBD Cohort 8
|
Drug: PF-06882961
Tablet, dose TBD, twice daily, Cohort 8, 28 days
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs) [From baseline to up to 35 days after last dose for a total of approximately 63 days]
Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality [From baseline to up to 14 days after last dose for a total of approximately 42 days]
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin).
- Number of Participants With Abnormal Vital Signs [From baseline to up to 14 days after last dose for a total of approximately 42 days]
Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg.
- Number of Participants With Abnormal Electrocardiogram (ECG) Interval [From baseline to up to 14 days after last dose for a total of approximately 42 days]
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline
Secondary Outcome Measures
- AUC24 and AUCtau of PF-06882961 on Day 1, Day 14 or 21 and Day 28 [0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28]
Area under the concentration-time profile from time zero to time 24 hours (AUC24) was calculated as AUCtau1 +AUCtau2, where AUCtau was area under the plasma concentration-time profile from time zero to time tau (tau1 = 0 to 10 hours and tau2=10 to 24 hours). AUCtau was determined using linear/log trapezoidal method.
- Maximum Plasma Concentration (Cmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28 [0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1, 14 or 21, and 28]
For BID dosing, parameters were calculated for both dosing intervals (0-10 hr = interval 1 and 10-24 hr = interval 2) and were displayed as Cmax1, Cmax2. Cmax1: maximum plasma concentration during the dosing interval τ1 =0 to 10 hours. Cmax2: maximum plasma concentration during the dosing interval τ2=10 to 24 hours.
- Time for Cmax (Tmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28 [0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28]
Time for Cmax, Cmax1 and Cmax2 (Tmax, Tmax1 and Tmax2) of PF-06293620 was observed directly from data as time of first occurrence.
- Terminal Half-life (t½) of PF-06882961 on Day 28 [0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 28]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Amount of Unchanged Drug Recovered in Urine Over 24 Hours (Ae24) of PF-06882961 on Day 28 [0 to 24 hours post-dose on Day 28]
Ae was the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval was 24 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL was the approximate specific gravity of urine.
- Ae24 (%) of PF-06882961 on Day 28 [0 to 24 hours post-dose on Day 28]
Percent of dose recovered in urine as unchanged drug. Ae24% = 100* Ae24/Dose
- Renal Clearance (CLr) of PF-06882961 on Day 28 [0 to 24 hours post-dose on Day 28]
CLr was calculated as Ae divided by AUCtau, where dosing interval is 24 hours.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Type 2 diabetes treated with a stable dose of metformin at least 500 mg
-
HbA1c value between 7.0 and 10.5%
Exclusion Criteria:
- Type 1 diabetes or secondary forms of diabetes
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anaheim Clinical Trials, LLC | Anaheim | California | United States | 92801 |
| 2 | Qps-Mra, Llc | South Miami | Florida | United States | 33143 |
| 3 | Qps-Mra,Llc | South Miami | Florida | United States | 33143 |
| 4 | Altasciences Clinical Kansas, Inc. | Overland Park | Kansas | United States | 66212 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03538743
Other Study ID Numbers:
- C3421002
First Posted:
May 29, 2018
Last Update Posted:
Jul 1, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID Slow Titration (ST) | PF-06882961 120mg QD | PF-06882961 200mg QD Controlled Release (CR) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally once daily (QD) or twice daily (BID) (dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. |
| Period Title: Overall Study | |||||||||
| STARTED | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| Received Treatment | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| COMPLETED | 25 | 9 | 8 | 8 | 9 | 9 | 9 | 8 | 7 |
| NOT COMPLETED | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | Total of all reporting groups |
| Overall Participants | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 | 98 |
| Age, Customized (Count of Participants) | ||||||||||
| 18-44 years |
1
4%
|
1
11.1%
|
1
11.1%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
4
4.1%
|
| 45-64 years |
19
76%
|
8
88.9%
|
6
66.7%
|
6
60%
|
8
88.9%
|
8
88.9%
|
7
77.8%
|
7
87.5%
|
8
80%
|
77
78.6%
|
| >=65 years |
5
20%
|
0
0%
|
2
22.2%
|
4
40%
|
1
11.1%
|
0
0%
|
2
22.2%
|
1
12.5%
|
2
20%
|
17
17.3%
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
13
52%
|
2
22.2%
|
6
66.7%
|
5
50%
|
5
55.6%
|
2
22.2%
|
5
55.6%
|
4
50%
|
5
50%
|
47
48%
|
| Male |
12
48%
|
7
77.8%
|
3
33.3%
|
5
50%
|
4
44.4%
|
7
77.8%
|
4
44.4%
|
4
50%
|
5
50%
|
51
52%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||
| Hispanic or Latino |
18
72%
|
6
66.7%
|
4
44.4%
|
7
70%
|
6
66.7%
|
4
44.4%
|
4
44.4%
|
6
75%
|
6
60%
|
61
62.2%
|
| Not Hispanic or Latino |
7
28%
|
3
33.3%
|
5
55.6%
|
3
30%
|
3
33.3%
|
5
55.6%
|
5
55.6%
|
2
25%
|
4
40%
|
37
37.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||
| White |
18
72%
|
7
77.8%
|
5
55.6%
|
8
80%
|
7
77.8%
|
6
66.7%
|
4
44.4%
|
8
100%
|
7
70%
|
70
71.4%
|
| Black or African American |
7
28%
|
2
22.2%
|
3
33.3%
|
2
20%
|
2
22.2%
|
3
33.3%
|
5
55.6%
|
0
0%
|
3
30%
|
27
27.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
| Age Range (Years) [Median (Full Range) ] | ||||||||||
| Median (Full Range) [Years] |
60.0
|
55.0
|
55.0
|
63.5
|
60.0
|
57.0
|
58.0
|
58.0
|
59.0
|
58.0
|
Outcome Measures
| Title | Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent. |
| Time Frame | From baseline to up to 35 days after last dose for a total of approximately 63 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of randomized study treatment. |
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. |
| Measure Participants | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| All-causality AE |
17
68%
|
6
66.7%
|
8
88.9%
|
10
100%
|
8
88.9%
|
8
88.9%
|
9
100%
|
8
100%
|
9
90%
|
| All-causality SAE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Treatment-related AE |
14
56%
|
4
44.4%
|
4
44.4%
|
10
100%
|
7
77.8%
|
8
88.9%
|
9
100%
|
8
100%
|
9
90%
|
| Treatment-related SAE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality |
|---|---|
| Description | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin). |
| Time Frame | From baseline to up to 14 days after last dose for a total of approximately 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of randomized study treatment. |
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. |
| Measure Participants | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| Count of Participants [Participants] |
24
96%
|
7
77.8%
|
8
88.9%
|
10
100%
|
8
88.9%
|
8
88.9%
|
9
100%
|
7
87.5%
|
10
100%
|
| Title | Number of Participants With Abnormal Vital Signs |
|---|---|
| Description | Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg. |
| Time Frame | From baseline to up to 14 days after last dose for a total of approximately 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of randomized study treatment. |
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. |
| Measure Participants | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| Supine SBP <90 mmHg |
3
12%
|
3
33.3%
|
2
22.2%
|
1
10%
|
3
33.3%
|
0
0%
|
3
33.3%
|
0
0%
|
1
10%
|
| Supine SBP increase >=30 mmHg |
4
16%
|
0
0%
|
0
0%
|
2
20%
|
3
33.3%
|
1
11.1%
|
2
22.2%
|
2
25%
|
1
10%
|
| Supine SBP decrease >=30 mmHg |
9
36%
|
2
22.2%
|
5
55.6%
|
3
30%
|
5
55.6%
|
3
33.3%
|
3
33.3%
|
5
62.5%
|
4
40%
|
| Supine DBP <50 mmHg |
1
4%
|
1
11.1%
|
2
22.2%
|
1
10%
|
1
11.1%
|
0
0%
|
2
22.2%
|
0
0%
|
0
0%
|
| Supine DBP increase >=20 mmHg |
1
4%
|
1
11.1%
|
1
11.1%
|
0
0%
|
4
44.4%
|
1
11.1%
|
2
22.2%
|
2
25%
|
1
10%
|
| Supine DBP decrease >=20 mmHg |
6
24%
|
2
22.2%
|
1
11.1%
|
2
20%
|
1
11.1%
|
3
33.3%
|
4
44.4%
|
2
25%
|
3
30%
|
| Supine pulse rate <40 bpm |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Supine pulse rate >120 bpm |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Abnormal Electrocardiogram (ECG) Interval |
|---|---|
| Description | ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline |
| Time Frame | From baseline to up to 14 days after last dose for a total of approximately 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of randomized study treatment. |
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. |
| Measure Participants | 25 | 9 | 9 | 10 | 9 | 9 | 9 | 8 | 10 |
| PR interval ≥300 msec |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| %Change in PR interval ≥25/50% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QRS duration ≥140 msec |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| %Change in QRS duration ≥50% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF interval >450 and ≤480 msec |
2
8%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF interval >480 and ≤500 msec |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF interval >500 msec |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Change in QTcF interval >30 and ≤60 msec |
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
| Change in QTcF interval >60 msec |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | AUC24 and AUCtau of PF-06882961 on Day 1, Day 14 or 21 and Day 28 |
|---|---|
| Description | Area under the concentration-time profile from time zero to time 24 hours (AUC24) was calculated as AUCtau1 +AUCtau2, where AUCtau was area under the plasma concentration-time profile from time zero to time tau (tau1 = 0 to 10 hours and tau2=10 to 24 hours). AUCtau was determined using linear/log trapezoidal method. |
| Time Frame | 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of PF-06882961 and who had at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 9 | 9 | 9 | 10 | 8 |
| AUC24 on Day 1 |
707.5
(43)
|
1502
(29)
|
645.8
(52)
|
666.1
(54)
|
178.7
(72)
|
324.0
(41)
|
393.9
(80)
|
184.6
(49)
|
| AUCtau1 on Day 1 |
288.1
(37)
|
741.4
(35)
|
279.7
(49)
|
260.3
(45)
|
74.50
(66)
|
147.7
(43)
|
NA
(NA)
|
NA
(NA)
|
| AUCtau2 on Day 1 |
414.8
(50)
|
678.5
(79)
|
364.9
(56)
|
401.9
(62)
|
103.7
(76)
|
176.4
(42)
|
NA
(NA)
|
NA
(NA)
|
| AUC24 on Day 14 or 21 |
853.8
(45)
|
2092
(91)
|
2988
(59)
|
8149
(84)
|
201.6
(63)
|
2660
(76)
|
1291
(68)
|
1204
(43)
|
| AUCtau1 on Day 14 or 21 |
348.6
(48)
|
880.3
(78)
|
1462
(70)
|
3772
(85)
|
85.57
(59)
|
957.3
(66)
|
NA
(NA)
|
NA
(NA)
|
| AUCtau2 on Day 14 or 21 |
500.1
(46)
|
1175
(110)
|
1517
(53)
|
4361
(89)
|
115.4
(68)
|
1693
(83)
|
NA
(NA)
|
NA
(NA)
|
| AUC24 on Day 28 |
876.7
(41)
|
1653
(55)
|
3171
(56)
|
8368
(79)
|
455.9
(66)
|
5973
(87)
|
4372
(31)
|
2723
(39)
|
| AUCtau1 on Day 28 |
331.1
(40)
|
671.1
(35)
|
1153
(44)
|
3534
(87)
|
190.8
(60)
|
2249
(88)
|
NA
(NA)
|
NA
(NA)
|
| AUCtau2 on Day 28 |
534.7
(46)
|
960.1
(73)
|
1970
(68)
|
4852
(74)
|
261.0
(72)
|
3668
(91)
|
NA
(NA)
|
NA
(NA)
|
| Title | Maximum Plasma Concentration (Cmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28 |
|---|---|
| Description | For BID dosing, parameters were calculated for both dosing intervals (0-10 hr = interval 1 and 10-24 hr = interval 2) and were displayed as Cmax1, Cmax2. Cmax1: maximum plasma concentration during the dosing interval τ1 =0 to 10 hours. Cmax2: maximum plasma concentration during the dosing interval τ2=10 to 24 hours. |
| Time Frame | 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1, 14 or 21, and 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants treated who had at least 1 measurable concentration value. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 9 | 9 | 9 | 10 | 8 |
| Cmax on Day 1 |
50.58
(40)
|
124.4
(51)
|
49.75
(50)
|
51.61
(50)
|
15.02
(70)
|
26.02
(39)
|
28.67
(87)
|
20.40
(29)
|
| Cmax1 on Day 1 |
42.69
(29)
|
119.1
(56)
|
45.01
(48)
|
36.51
(43)
|
12.82
(58)
|
24.06
(42)
|
NA
(NA)
|
NA
(NA)
|
| Cmax2 on Day 1 |
40.63
(66)
|
68.77
(51)
|
42.33
(59)
|
44.97
(61)
|
13.98
(75)
|
21.64
(41)
|
NA
(NA)
|
NA
(NA)
|
| Cmax on Day 14 or 21 |
65.78
(35)
|
149.8
(88)
|
253.6
(76)
|
788.4
(89)
|
18.63
(47)
|
188.5
(57)
|
98.11
(54)
|
100.7
(35)
|
| Cmax1 on Day 14 or 21 |
55.00
(43)
|
130.2
(85)
|
235.1
(84)
|
682.7
(92)
|
15.31
(50)
|
143.0
(71)
|
NA
(NA)
|
NA
(NA)
|
| Cmax2 on Day 14 or 21 |
63.89
(36)
|
127.9
(86)
|
202.8
(50)
|
505.3
(93)
|
17.16
(58)
|
178.4
(56)
|
NA
(NA)
|
NA
(NA)
|
| Cmax on Day 28 |
81.56
(32)
|
133.7
(69)
|
328.8
(49)
|
685.2
(87)
|
38.38
(58)
|
437.6
(94)
|
303.9
(32)
|
192.2
(52)
|
| Cmax1 on Day 28 |
50.24
(44)
|
103.8
(50)
|
197.9
(51)
|
649.2
(90)
|
30.42
(52)
|
357.1
(84)
|
NA
(NA)
|
NA
(NA)
|
| Cmax2 on Day 28 |
74.22
(37)
|
117.2
(63)
|
306.5
(49)
|
617.9
(93)
|
35.01
(56)
|
410.3
(90)
|
NA
(NA)
|
NA
(NA)
|
| Title | Time for Cmax (Tmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28 |
|---|---|
| Description | Time for Cmax, Cmax1 and Cmax2 (Tmax, Tmax1 and Tmax2) of PF-06293620 was observed directly from data as time of first occurrence. |
| Time Frame | 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 9 | 9 | 9 | 10 | 8 |
| Tmax on Day 1 |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
13.0
|
3.00
|
| Tmax1 on Day 1 |
4.00
|
4.00
|
2.00
|
4.00
|
2.00
|
2.00
|
NA
|
NA
|
| Tmax2 on Day 1 |
14.0
|
14.0
|
14.0
|
14.0
|
12.0
|
14.0
|
NA
|
NA
|
| Tmax on Day 14 or 21 |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
12.0
|
6.00
|
| Tmax1 on Day 14 or 21 |
4.00
|
4.00
|
1.05
|
1.54
|
6.00
|
6.00
|
NA
|
NA
|
| Tmax2 on Day 14 or 21 |
13.0
|
13.0
|
12.0
|
12.0
|
12.0
|
14.0
|
NA
|
NA
|
| Tmax on Day 28 |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
14.0
|
10.0
|
| Tmax1 on Day 28 |
5.00
|
3.00
|
6.00
|
4.00
|
4.00
|
6.00
|
NA
|
NA
|
| Tmax2 on Day 28 |
12.0
|
12.0
|
12.0
|
12.0
|
12.0
|
12.0
|
NA
|
NA
|
| Title | Terminal Half-life (t½) of PF-06882961 on Day 28 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 9 | 9 | 9 | 10 | 8 |
| Mean (Standard Deviation) [hours] |
5.100
(1.2186)
|
5.067
(0.75593)
|
4.681
(0.59504)
|
6.203
(2.3505)
|
8.090
(3.3234)
|
6.730
(2.5056)
|
5.773
(1.4876)
|
4.954
(0.58819)
|
| Title | Amount of Unchanged Drug Recovered in Urine Over 24 Hours (Ae24) of PF-06882961 on Day 28 |
|---|---|
| Description | Ae was the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval was 24 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL was the approximate specific gravity of urine. |
| Time Frame | 0 to 24 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of PF-06882961 and who have at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 8 | 9 | 7 | 7 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [microgram] |
17.25
(36)
|
33.60
(69)
|
41.16
(243)
|
NA
(NA)
|
14.97
(67)
|
62.63
(439)
|
72.98
(38)
|
49.09
(97)
|
| Title | Ae24 (%) of PF-06882961 on Day 28 |
|---|---|
| Description | Percent of dose recovered in urine as unchanged drug. Ae24% = 100* Ae24/Dose |
| Time Frame | 0 to 24 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of PF-06882961 and who have at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 8 | 9 | 7 | 7 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage] |
0.05747
(36)
|
0.03360
(69)
|
0.02942
(242)
|
NA
(NA)
|
0.07483
(67)
|
0.02607
(439)
|
0.03652
(38)
|
0.04094
(97)
|
| Title | Renal Clearance (CLr) of PF-06882961 on Day 28 |
|---|---|
| Description | CLr was calculated as Ae divided by AUCtau, where dosing interval is 24 hours. |
| Time Frame | 0 to 24 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of PF-06882961 and who have at least 1 of the PK parameters of interest. |
| Arm/Group Title | PF-06882961 15mg BID (Cohort 1) | PF-06882961 50mg BID (Cohort 2) | PF-06882961 70mg BID (Cohort 3) | PF-06882961 120mg BID (Cohort 4) | PF-06882961 10mg BID (Cohort 5) | PF-06882961 120mg BID ST (Cohort 6) | PF-06882961 200mg QD CR (Cohort 7) | PF-06882961 120mg QD (Cohort 8) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. |
| Measure Participants | 9 | 10 | 9 | 8 | 9 | 7 | 7 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/min] |
0.3273
(18)
|
0.3385
(18)
|
0.3094
(70)
|
NA
(NA)
|
0.5470
(26)
|
0.2006
(228)
|
0.2895
(21)
|
0.3178
(73)
|
Adverse Events
| Time Frame | Baseline up to 35 days after last dose for a total of approximately 63 days | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and non-serious event during the study. | |||||||||||||||||
| Arm/Group Title | Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR | |||||||||
| Arm/Group Description | Placebo matched to PF-06882961 was administered orally QD or BID(dependent upon corresponding study treatment regimen) for a total of 28 days. | PF-06882961 tablet was administered orally at 5 mg BID from Day 1 to Day 14 followed by a dose of 10 mg BID from Day 15 to Day 28. | PF-06882961 tablet was administered orally at 15 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 50 mg BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-3), 40 mg (Day 4-6), 50 mg (Day 7-9) and 70 mg (Day 10-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 20 mg (Day 1-2), 40 mg (Day 3-4), 60 mg (Day 5-6), 80 mg (Day 7-9), 100 mg (Day 10-12) and 120 mg (Day 13-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-4), 20 mg (Day 5-8), 40 mg (Day 9-12), 60 mg (Day 13-16), 80 mg (Day 17-20), 100 mg (Day 21-24) and 120 mg (Day 25-28) BID for a total of 28 days. | PF-06882961 tablet was administered orally at 10 mg (Day 1-2), 20 mg (Day 3-4), 30 mg (Day 5-6), 40 mg (Day 7-10), 60 mg (Day 11-14), 80 mg (Day 15-18), 100 mg (Day 19-22) and 120 mg (Day 23-28) QD for a total of 28 days. | PF-06882961 CR tablet was administered orally at 50 mg (Day 1-7), 100 mg (Day 8-14), 150 mg (Day 15-21) and 200 mg (Day 22-28) QD for a total of 28 days. | |||||||||
All Cause Mortality |
||||||||||||||||||
| Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Acute myocardial infarction | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Placebo | PF-06882961 10mg BID | PF-06882961 15mg BID | PF-06882961 50mg BID | PF-06882961 70mg BID | PF-06882961 120mg BID | PF-06882961 120mg BID ST | PF-06882961 120mg QD | PF-06882961 200mg QD CR | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/25 (60%) | 6/9 (66.7%) | 8/9 (88.9%) | 10/10 (100%) | 8/9 (88.9%) | 8/9 (88.9%) | 9/9 (100%) | 8/8 (100%) | 9/10 (90%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/25 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Ear and labyrinth disorders | ||||||||||||||||||
| Ear discomfort | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Tinnitus | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Dry eye | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 2/10 (20%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Vision blurred | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 2/10 (20%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal discomfort | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 2/9 (22.2%) | 2/9 (22.2%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Abdominal distension | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 3/9 (33.3%) | 0/9 (0%) | 0/9 (0%) | 2/8 (25%) | 0/10 (0%) | |||||||||
| Abdominal pain | 0/25 (0%) | 1/9 (11.1%) | 1/9 (11.1%) | 1/10 (10%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Change of bowel habit | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Constipation | 3/25 (12%) | 2/9 (22.2%) | 2/9 (22.2%) | 1/10 (10%) | 2/9 (22.2%) | 1/9 (11.1%) | 6/9 (66.7%) | 1/8 (12.5%) | 2/10 (20%) | |||||||||
| Diarrhoea | 5/25 (20%) | 0/9 (0%) | 3/9 (33.3%) | 2/10 (20%) | 3/9 (33.3%) | 4/9 (44.4%) | 1/9 (11.1%) | 2/8 (25%) | 4/10 (40%) | |||||||||
| Dyspepsia | 4/25 (16%) | 0/9 (0%) | 0/9 (0%) | 5/10 (50%) | 4/9 (44.4%) | 4/9 (44.4%) | 7/9 (77.8%) | 3/8 (37.5%) | 5/10 (50%) | |||||||||
| Eructation | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 2/10 (20%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Flatulence | 1/25 (4%) | 0/9 (0%) | 0/9 (0%) | 0/0 (NaN) | 0/0 (NaN) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Gastrointestinal motility disorder | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Gastrooesophageal reflux disease | 1/25 (4%) | 0/9 (0%) | 0/9 (0%) | 1/10 (10%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/10 (10%) | |||||||||
| Gingivitis ulcerative | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Nausea | 4/25 (16%) | 0/9 (0%) | 2/9 (22.2%) | 7/10 (70%) | 3/9 (33.3%) | 8/9 (88.9%) | 9/9 (100%) | 7/8 (87.5%) | 8/10 (80%) | |||||||||
| Retching | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Toothache | 0/25 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Vomiting | 2/25 (8%) | 0/9 (0%) | 0/9 (0%) | 2/10 (20%) | 2/9 (22.2%) | 7/9 (77.8%) | 7/9 (77.8%) | 3/8 (37.5%) | 3/10 (30%) | |||||||||
| General disorders | ||||||||||||||||||
| Asthenia | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Chest pain | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Early satiety | 2/25 (8%) | 1/9 (11.1%) | 0/9 (0%) | 5/10 (50%) | 1/9 (11.1%) | 0/9 (0%) | 2/9 (22.2%) | 1/8 (12.5%) | 2/10 (20%) | |||||||||
| Fatigue | 1/25 (4%) | 0/9 (0%) | 0/9 (0%) | 3/10 (30%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Tooth infection | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Upper respiratory tract infection | 2/25 (8%) | 1/9 (11.1%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Fall | 0/25 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Limb injury | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Road traffic accident | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Skin laceration | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 1/10 (10%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Alanine aminotransferase increased | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 2/10 (20%) | |||||||||
| Aspartate aminotransferase increased | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Blood creatinine increased | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Thyroid function test abnormal | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Weight decreased | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 1/10 (10%) | 1/9 (11.1%) | 2/9 (22.2%) | 1/9 (11.1%) | 2/8 (25%) | 1/10 (10%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Decreased appetite | 1/25 (4%) | 0/9 (0%) | 0/9 (0%) | 1/10 (10%) | 1/9 (11.1%) | 6/9 (66.7%) | 2/9 (22.2%) | 3/8 (37.5%) | 5/10 (50%) | |||||||||
| Hypoglycaemia | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Back pain | 0/25 (0%) | 0/9 (0%) | 2/9 (22.2%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Musculoskeletal pain | 0/25 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Myalgia | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Pain in extremity | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Dizziness | 1/25 (4%) | 0/9 (0%) | 0/9 (0%) | 2/10 (20%) | 2/9 (22.2%) | 2/9 (22.2%) | 2/9 (22.2%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Headache | 8/25 (32%) | 0/9 (0%) | 1/9 (11.1%) | 5/10 (50%) | 2/9 (22.2%) | 0/9 (0%) | 0/9 (0%) | 4/8 (50%) | 3/10 (30%) | |||||||||
| Paraesthesia | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Tremor | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Dysuria | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 1/10 (10%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Epistaxis | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Hiccups | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Nasal congestion | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Oropharyngeal pain | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Acne | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 1/10 (10%) | |||||||||
| Blister | 0/25 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Dermatitis contact | 2/25 (8%) | 0/9 (0%) | 1/9 (11.1%) | 1/10 (10%) | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/10 (0%) | |||||||||
| Hyperhidrosis | 0/25 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/10 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/9 (0%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Rash | 1/25 (4%) | 0/9 (0%) | 1/9 (11.1%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 2/9 (22.2%) | 0/8 (0%) | 0/10 (0%) | |||||||||
| Skin irritation | 0/25 (0%) | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/9 (0%) | 0/9 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/10 (0%) | |||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03538743
Other Study ID Numbers:
- C3421002
First Posted:
May 29, 2018
Last Update Posted:
Jul 1, 2020
Last Verified:
Jun 1, 2020