Trial Outcomes & Findings for Study To Test Whether PF-00547659 Is Safe And Improves Disease Symptoms In Patients With Crohn's Disease (NCT NCT01276509)
NCT ID: NCT01276509
Last Updated: 2021-06-03
Results Overview
Crohn's Disease Activity Index (CDAI) is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. CDAI response rate at week 8 and week 12 was measured between the investigational product group and the placebo group.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
265 participants
Primary outcome timeframe
Week 8 and week 12
Results posted on
2021-06-03
Participant Flow
In total, 265 participants were randomized and 262 entered the study and received study treatment.
Participant milestones
| Measure |
PF-00547659 22.5 mg
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
66
|
65
|
68
|
63
|
|
Overall Study
COMPLETED
|
53
|
53
|
63
|
58
|
|
Overall Study
NOT COMPLETED
|
13
|
12
|
5
|
5
|
Reasons for withdrawal
| Measure |
PF-00547659 22.5 mg
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
8
|
4
|
3
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
1
|
2
|
|
Overall Study
Pregnancy
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
0
|
0
|
|
Overall Study
Other
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study To Test Whether PF-00547659 Is Safe And Improves Disease Symptoms In Patients With Crohn's Disease
Baseline characteristics by cohort
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
Total
n=262 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.3 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
34.4 years
STANDARD_DEVIATION 10.7 • n=7 Participants
|
35.9 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
34.4 years
STANDARD_DEVIATION 11.1 • n=4 Participants
|
35.5 years
STANDARD_DEVIATION 11.5 • n=21 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
156 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
106 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Week 8 and week 12Population: The full analysis set included all randomized participants who received at least one dose of study medication.
Crohn's Disease Activity Index (CDAI) is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. CDAI response rate at week 8 and week 12 was measured between the investigational product group and the placebo group.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate
Week 8 (n =50, 55, 62, 56)
|
52.7 Percentage of Participants
|
60.1 Percentage of Participants
|
62.7 Percentage of Participants
|
47.7 Percentage of Participants
|
|
Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate
Week 12 (n = 51, 49, 61, 54)
|
62.0 Percentage of Participants
|
64.7 Percentage of Participants
|
57.5 Percentage of Participants
|
58.6 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 0-12Population: The safety analysis set included all participants who received at least 1 dose of study medication.
Number of participants with adverse events (AEs), withdrawals due to AEs and Serious AEs (SAEs) were reported.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Withdrawal due to AEs (treatment related)
|
5 Number of participants
|
2 Number of participants
|
0 Number of participants
|
1 Number of participants
|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Participants with AEs (all causalities)
|
57 Number of participants
|
51 Number of participants
|
54 Number of participants
|
54 Number of participants
|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Participants with AEs (treatment related)
|
20 Number of participants
|
24 Number of participants
|
29 Number of participants
|
22 Number of participants
|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Withdrawal due to AEs (all causalities)
|
9 Number of participants
|
8 Number of participants
|
4 Number of participants
|
3 Number of participants
|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Participants with SAEs (all causalities)
|
11 Number of participants
|
9 Number of participants
|
11 Number of participants
|
5 Number of participants
|
|
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo
Participants with SAEs (treatment related)
|
4 Number of participants
|
4 Number of participants
|
2 Number of participants
|
2 Number of participants
|
SECONDARY outcome
Timeframe: Week 0-12Population: The safety analysis set included all participants who received at least 1 dose of study medication.
Number of adverse events (all causalities and treatment related) was reported between the investigational product groups and the placebo group.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo
Number of AEs (all causalities)
|
175 events
|
192 events
|
192 events
|
141 events
|
|
Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo
Number of AEs (treatment related)
|
40 events
|
55 events
|
64 events
|
40 events
|
SECONDARY outcome
Timeframe: Weeks 8 and week 12Population: The full analysis set included all randomized participants who received at least one dose of study medication.
Percentage of participants with a CDAI remission (defined as a CDAI reduction to \<150 points).
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission
Week 8 (n = 50, 56, 62, 57)
|
29.1 Percentage of Participants
|
23.8 Percentage of Participants
|
26.9 Percentage of Participants
|
16.7 Percentage of Participants
|
|
Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission
Week 12 (n= 51, 49, 61, 55)
|
26.8 Percentage of Participants
|
28.5 Percentage of Participants
|
29.6 Percentage of Participants
|
23.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 2, 4, 6, 8, 10 and 12Population: The full analysis set included all randomized participants who received at least one dose of study medication.
Percentage of participants with Crohn's Disease Activity Index (CDAI)-70 response were reported.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 6 (n =56, 54, 64, 58)
|
45.3 Percentage of Participants
Interval 31.1 to 60.3
|
53.4 Percentage of Participants
Interval 38.2 to 67.9
|
47.5 Percentage of Participants
Interval 33.3 to 62.1
|
48.0 Percentage of Participants
Interval 33.5 to 62.9
|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 2 (n = 64, 60, 63, 60)
|
35.1 Percentage of Participants
Interval 22.8 to 49.6
|
22.4 Percentage of Participants
Interval 12.9 to 36.0
|
33.8 Percentage of Participants
Interval 21.6 to 48.5
|
35.5 Percentage of Participants
Interval 22.9 to 50.5
|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 4 (n = 58, 60, 65, 58)
|
38.0 Percentage of Participants
Interval 24.9 to 53.2
|
39.5 Percentage of Participants
Interval 26.3 to 54.4
|
36.2 Percentage of Participants
Interval 23.7 to 51.0
|
38.3 Percentage of Participants
Interval 25.1 to 53.5
|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 8 (n =50, 55, 62, 56)
|
52.7 Percentage of Participants
Interval 37.2 to 67.7
|
60.1 Percentage of Participants
Interval 44.9 to 73.6
|
62.7 Percentage of Participants
Interval 47.9 to 75.4
|
47.7 Percentage of Participants
Interval 33.1 to 62.7
|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 10 (n =50, 48, 60, 52)
|
67.4 Percentage of Participants
Interval 52.0 to 79.7
|
58.2 Percentage of Participants
Interval 42.3 to 72.6
|
61.6 Percentage of Participants
Interval 46.8 to 74.6
|
53.0 Percentage of Participants
Interval 37.6 to 67.8
|
|
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time
Week 12 (n = 51, 49, 61, 54)
|
62.0 Percentage of Participants
Interval 46.5 to 75.3
|
64.7 Percentage of Participants
Interval 48.9 to 77.8
|
57.5 Percentage of Participants
Interval 42.6 to 71.2
|
58.6 Percentage of Participants
Interval 43.3 to 72.4
|
SECONDARY outcome
Timeframe: Week 2, 4, 6, 8, 10 and 12Population: The full analysis set included all randomized participants who received at least one dose of study medication.
Percentage of participants with Crohn's Disease Activity Index (CDAI)-100 response were reported.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 Participants
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 2 (n = 64, 60, 63, 60)
|
19.3 Percentage of Participants
Interval 10.6 to 32.6
|
18.4 Percentage of Participants
Interval 9.9 to 31.7
|
20.0 Percentage of Participants
Interval 11.0 to 33.6
|
18.5 Percentage of Participants
Interval 9.9 to 31.9
|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 4 (n = 58, 60 ,65, 58)
|
29.2 Percentage of Participants
Interval 17.5 to 44.6
|
32.3 Percentage of Participants
Interval 20.0 to 47.5
|
28.2 Percentage of Participants
Interval 17.0 to 43.0
|
29.5 Percentage of Participants
Interval 17.7 to 44.9
|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 6 (n =56, 54, 64, 58)
|
40.6 Percentage of Participants
Interval 26.6 to 56.4
|
42.6 Percentage of Participants
Interval 28.2 to 58.5
|
40.4 Percentage of Participants
Interval 26.8 to 55.8
|
39.3 Percentage of Participants
Interval 25.5 to 55.0
|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 8 (n = 50, 55, 62, 56)
|
50.5 Percentage of Participants
Interval 34.8 to 66.2
|
48.3 Percentage of Participants
Interval 33.3 to 63.7
|
57.0 Percentage of Participants
Interval 41.8 to 71.0
|
41.4 Percentage of Participants
Interval 27.2 to 57.3
|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 10 (n = 50, 48, 62, 52)
|
53.2 Percentage of Participants
Interval 37.3 to 68.5
|
47.4 Percentage of Participants
Interval 31.8 to 63.5
|
50.9 Percentage of Participants
Interval 35.9 to 65.7
|
43.6 Percentage of Participants
Interval 28.7 to 59.7
|
|
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer
Week 12 (n = 51, 49, 61, 54)
|
56.0 Percentage of Participants
Interval 40.1 to 70.7
|
47.7 Percentage of Participants
Interval 32.2 to 63.7
|
53.8 Percentage of Participants
Interval 38.7 to 68.4
|
44.4 Percentage of Participants
Interval 29.6 to 60.2
|
SECONDARY outcome
Timeframe: Day 1, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36Population: The safety analysis set included all participants who receive at least 1 dose of PF-00547659. Participants in placebo arm were not included in this analysis.
Confirmed cumulative incidence of anti-drug antibodies development to PF-00547659
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=66 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Day 1 (n =46, 52, 53)
|
3 events
|
5 events
|
1 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 4 (n = 55, 52, 55)
|
2 events
|
4 events
|
2 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 8 (n = 44, 47, 56)
|
1 events
|
1 events
|
1 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 12 (n = 47, 51, 51)
|
3 events
|
5 events
|
1 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 20 (n = 4, 3, 1)
|
0 events
|
0 events
|
0 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 28 (n = 8, 1, 1)
|
1 events
|
0 events
|
0 events
|
—
|
|
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)
Week 36 (n = 6, 2, 1)
|
0 events
|
0 events
|
0 events
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to area under the concentration-time profile (AUC), clearance (CL) and half life were estimated using data pooled from both typical and additional PK groups. AUCinf is area under the concentration time profile from time zero extrapolated to infinite time.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=6 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=8 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=6 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)
|
615300 µg•hr/mL
Geometric Coefficient of Variation 63
|
4464000 µg•hr/mL
Geometric Coefficient of Variation 28
|
13760000 µg•hr/mL
Geometric Coefficient of Variation 49
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, and 28Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. AUCtau is area under the concentration time profile from time zero to time tau, the dosing interval, where tau = 672 hours (4 weeks)
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=7 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=10 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=12 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero to Time Tau (AUCtau)
|
549500 µg•hr/mL
Geometric Coefficient of Variation 53
|
4214000 µg•hr/mL
Geometric Coefficient of Variation 31
|
10850000 µg•hr/mL
Geometric Coefficient of Variation 45
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Cmax is maximum observed concentration.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=7 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=10 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=13 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Maximum Observed Concentration (Cmax)
|
1756 µg/mL
Geometric Coefficient of Variation 45
|
10800 µg/mL
Geometric Coefficient of Variation 22
|
24100 µg/mL
Geometric Coefficient of Variation 47
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Tmax is time for Cmax.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=7 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=10 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=13 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Time for Cmax (Tmax)
|
140 Hours
Full Range 45 • Interval 43.9 to 333.0
|
143 Hours
Full Range 22 • Interval 44.9 to 171.0
|
165 Hours
Full Range 47 • Interval 51.7 to 214.0
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Thalf is terminal half life.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=6 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=8 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=6 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Terminal Half Life (Thalf)
|
4.977 Day
Standard Deviation 2.8435
|
8.770 Day
Standard Deviation 2.3571
|
12.22 Day
Standard Deviation 3.8306
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252Population: All participants who received at least 1 dose of investigational product and had data for at least 1 PK concentration were included in the PK concentration analysis.
The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. CL/F is apparent clearance.
Outcome measures
| Measure |
PF-00547659 22.5 mg
n=6 Participants
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=8 Participants
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=6 Participants
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
The Pharmacokinetics (PK) of Total PF-00547659 - Apparent Clearance (CL/F)
|
36.54 mL/hr
Geometric Coefficient of Variation 63
|
16.79 mL/hr
Geometric Coefficient of Variation 28
|
16.38 mL/hr
Geometric Coefficient of Variation 49
|
—
|
Adverse Events
PF-00547659 22.5 mg
Serious events: 12 serious events
Other events: 36 other events
Deaths: 0 deaths
PF-00547659 75 mg
Serious events: 11 serious events
Other events: 32 other events
Deaths: 0 deaths
PF-00547659 225 mg
Serious events: 11 serious events
Other events: 42 other events
Deaths: 0 deaths
Placebo
Serious events: 6 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PF-00547659 22.5 mg
n=66 participants at risk
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 participants at risk
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 participants at risk
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 participants at risk
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Crohn's disease
|
7.6%
5/66
|
9.2%
6/65
|
5.9%
4/68
|
6.3%
4/63
|
|
Gastrointestinal disorders
Fistula of small intestine
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Rectal stenosis
|
0.00%
0/66
|
0.00%
0/65
|
0.00%
0/68
|
1.6%
1/63
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/66
|
1.5%
1/65
|
2.9%
2/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Subileus
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
General disorders
Chest pain
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
General disorders
Pyrexia
|
0.00%
0/66
|
1.5%
1/65
|
1.5%
1/68
|
1.6%
1/63
|
|
Hepatobiliary disorders
Cholecystitis
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Anal abscess
|
0.00%
0/66
|
1.5%
1/65
|
1.5%
1/68
|
1.6%
1/63
|
|
Infections and infestations
Appendicitis
|
3.0%
2/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Liver abscess
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Infections and infestations
Rectal abscess
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Sepsis
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
1/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
1.5%
1/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Nervous system disorders
Cerebellar infarction
|
0.00%
0/66
|
1.5%
1/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Nervous system disorders
Headache
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/66
|
0.00%
0/65
|
1.5%
1/68
|
0.00%
0/63
|
Other adverse events
| Measure |
PF-00547659 22.5 mg
n=66 participants at risk
PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.
|
PF-00547659 75 mg
n=65 participants at risk
PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks
|
PF-00547659 225 mg
n=68 participants at risk
PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks
|
Placebo
n=63 participants at risk
Placebo delivered SC, 3 doses separated by 4 weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
10.6%
7/66
|
1.5%
1/65
|
5.9%
4/68
|
4.8%
3/63
|
|
Gastrointestinal disorders
Crohn's disease
|
7.6%
5/66
|
10.8%
7/65
|
1.5%
1/68
|
7.9%
5/63
|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
1/66
|
6.2%
4/65
|
1.5%
1/68
|
1.6%
1/63
|
|
Gastrointestinal disorders
Nausea
|
10.6%
7/66
|
6.2%
4/65
|
7.4%
5/68
|
11.1%
7/63
|
|
Gastrointestinal disorders
Proctalgia
|
1.5%
1/66
|
6.2%
4/65
|
1.5%
1/68
|
0.00%
0/63
|
|
Gastrointestinal disorders
Vomiting
|
6.1%
4/66
|
4.6%
3/65
|
4.4%
3/68
|
6.3%
4/63
|
|
General disorders
Fatigue
|
7.6%
5/66
|
6.2%
4/65
|
2.9%
2/68
|
4.8%
3/63
|
|
General disorders
Injection site erythema
|
1.5%
1/66
|
6.2%
4/65
|
2.9%
2/68
|
4.8%
3/63
|
|
General disorders
Oedema peripheral
|
0.00%
0/66
|
1.5%
1/65
|
7.4%
5/68
|
0.00%
0/63
|
|
General disorders
Pyrexia
|
7.6%
5/66
|
9.2%
6/65
|
11.8%
8/68
|
11.1%
7/63
|
|
Infections and infestations
Influenza
|
6.1%
4/66
|
3.1%
2/65
|
1.5%
1/68
|
1.6%
1/63
|
|
Infections and infestations
Nasopharyngitis
|
4.5%
3/66
|
6.2%
4/65
|
7.4%
5/68
|
7.9%
5/63
|
|
Infections and infestations
Urinary tract infection
|
3.0%
2/66
|
1.5%
1/65
|
4.4%
3/68
|
7.9%
5/63
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
4.5%
3/66
|
0.00%
0/65
|
0.00%
0/68
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.6%
5/66
|
9.2%
6/65
|
7.4%
5/68
|
4.8%
3/63
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/66
|
1.5%
1/65
|
5.9%
4/68
|
3.2%
2/63
|
|
Nervous system disorders
Headache
|
9.1%
6/66
|
4.6%
3/65
|
11.8%
8/68
|
9.5%
6/63
|
|
Skin and subcutaneous tissue disorders
Erythema
|
4.5%
3/66
|
3.1%
2/65
|
5.9%
4/68
|
3.2%
2/63
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER