Pharmacokinetics And Relative Bioavailability Of Bococizumab (PF-04950615; RN316) When Administered To The Abdomen, Thigh Or Upper Arm
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02043301
Collaborator
(none)
75
6
3
7
12.5
1.8
Study Details
Study Description
Brief Summary
This study aims to characterize the single dose pharmacokinetics of PF-04950616 following subcutaneous injection to the abdomen, upper arm or the thigh.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
75 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, PARALLEL GROUP STUDY TO ASSESS INJECTION SITE RELATIVE BIOAVAILABILITY OF PF-04950615 FOLLOWING SUBCUTANEOUS ADMINISTRATION IN ADULT SUBJECTS WITH HYPERCHOLESTEROLEMIA
Actual Study Start Date
:
Apr 1, 2014
Actual Primary Completion Date
:
Nov 1, 2014
Actual Study Completion Date
:
Nov 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Single 150 mg PF-04950615 dose administered to the abdomen
|
Biological: Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the abdomen
|
| Experimental: Single 150 mg PF-04950615 dose administered to the upper arm
|
Biological: Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the upper arm
|
| Experimental: Single 150 mg PF-04950615 dose administered to the thigh
|
Biological: Bococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the thigh
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.
- Maximum Observed Plasma Concentration (Cmax) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
Maximum observed concentration.
Secondary Outcome Measures
- Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
Time for maximum observed concentration.
- Apparent Clearance (CL/F) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
Apparent clearance following subcutaneous administration.
- Apparent Volume of Distribution (Vz/F) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
Apparent volume of distribution following subcutaneous administration.
- Terminal Elimination Half-Life (t1/2) [Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.]
Terminal elimination half-life following subcutaneous administration.
- Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
Maximum LDL-C response using absolute on trial LDL-C data
- Emax: Change From Baseline [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
LDL-C Emax expressed as change from baseline.
- Emax: Percent Change From Baseline [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
LDL-C Emax expressed as percent change from baseline.
- Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
Time to LDL-C Emax
- Area Under the LDL-C Effect Curve (AUEC): Absolute Value [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value
- AUEC: Change From Baseline [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed as change from baseline
- AUEC: Percent Change From Baseline [Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination]
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline.
- Number of Participants With Injection Site Reactions (ISRs) by Severity [Day 1 to Day 85]
Acute injection site reactions (e.g, pain, pruritus, induration) were captured as adverse events (AEs). Intensity of the AE was described as mild (does not interfere with usual function), moderate (interferes to some extent with usual function), or severe (interferes significantly with participant's usual function).
- Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) [Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination]
A participant is ADA positive if ADA titer (log2) >=6.23. A participant is nAb positive if nAb titer (log2) >=4.32.
- Anti-Drug Antibody (ADA) Titer [Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination]
ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
- Neutralizing Antibody (nAb) Titer [Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination]
nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male and female subjects 18 to 65 years of age.
-
Body Mass Index (BMI) ≤ 33 kg/m2, and total body weight of 60 kg to 90 kg (132 lbs to 198 lbs).
-
Fasting LDL-C must be > 130 mg/dL (borderline high per NCEP ATP III criteria) at two qualifying visits: initial screening (Days -28 to -14) and Day -7.
Exclusion Criteria:
-
Poorly controlled type 1 or type 2 diabetes mellitus (HbA1c > 9.0%).
-
History of a cardiovascular or cerebrovascular event (eg, MI, stroke, TIA) or related procedure (eg, angioplasty) during the past year.
-
Subjects who meet the New York Heart Association (NYHA) criteria for congestive heart failure (CHF) classes III or IV.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anaheim Clinical Trials, LLC | Anaheim | California | United States | 92801 |
| 2 | Miami Research Associates | South Miami | Florida | United States | 33143 |
| 3 | MRA Clinical Research, LLC | South Miami | Florida | United States | 33143 |
| 4 | Vince & Associates Clinical Research, Inc. | Overland Park | Kansas | United States | 66211 |
| 5 | Vince & Associates Clinical Research, Inc. | Overland Park | Kansas | United States | 66212 |
| 6 | Clinical Trials of Texas, Inc. | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02043301
Other Study ID Numbers:
- B1481024
First Posted:
Jan 23, 2014
Last Update Posted:
May 31, 2019
Last Verified:
Feb 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Seventy-five (75) participants were enrolled and randomized in a 1:1:1 ratio to receive a single dose of Treatment A (PF-04950615 [hereafter referred to as bococizumab] 150 mg subcutaneously [SC] to the abdomen), Treatment B (bococizumab 150 mg SC to the thigh), or Treatment C (bococizumab 150 mg SC to the upper arm). |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Period Title: Overall Study | |||
| STARTED | 25 | 25 | 25 |
| COMPLETED | 25 | 24 | 25 |
| NOT COMPLETED | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. | Total of all reporting groups |
| Overall Participants | 25 | 25 | 25 | 75 |
| Age, Customized (Count of Participants) | ||||
| Less than (<) 18 years |
0
(11.7)
0%
|
0
(7.5)
0%
|
0
(9.6)
0%
|
0
0%
|
| 18-44 years |
11
44%
|
7
28%
|
8
32%
|
26
34.7%
|
| 45-64 years |
13
52%
|
18
72%
|
17
68%
|
48
64%
|
| Greater than or equal to (>=) 65 years |
1
4%
|
0
0%
|
0
0%
|
1
1.3%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
10
40%
|
12
48%
|
13
52%
|
35
46.7%
|
| Male |
15
60%
|
13
52%
|
12
48%
|
40
53.3%
|
Outcome Measures
| Title | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) |
|---|---|
| Description | AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic (PK) parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 24 | 25 | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*day/milliliter (mcg*day/mL)] |
175.9
(53)
|
198.9
(30)
|
160.3
(33)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | Thigh (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 120.96 | |
| Confidence Interval |
(2-Sided) 90% 101.99 to 143.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | Upper Arm (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 94.93 | |
| Confidence Interval |
(2-Sided) 90% 80.20 to 112.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | Maximum observed concentration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [mcg/mL] |
9.68
(51)
|
11.89
(30)
|
8.14
(32)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | Thigh (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 127.65 | |
| Confidence Interval |
(2-Sided) 90% 107.19 to 152.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | Upper Arm (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 86.16 | |
| Confidence Interval |
(2-Sided) 90% 72.49 to 102.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) |
|---|---|
| Description | AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [mcg*day/mL] |
158.8
(65)
|
192.5
(31)
|
152.6
(36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | Thigh (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 129.98 | |
| Confidence Interval |
(2-Sided) 90% 106.76 to 158.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | Upper Arm (Test) versus Abdomen (Reference) | |
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 100.27 | |
| Confidence Interval |
(2-Sided) 90% 82.54 to 121.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | Time for maximum observed concentration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Median (Full Range) [days] |
5.04
|
4.25
|
6.93
|
| Title | Apparent Clearance (CL/F) |
|---|---|
| Description | Apparent clearance following subcutaneous administration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 24 | 25 | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [liters per day] |
0.8521
(53)
|
0.7545
(30)
|
0.9352
(33)
|
| Title | Apparent Volume of Distribution (Vz/F) |
|---|---|
| Description | Apparent volume of distribution following subcutaneous administration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 24 | 25 | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [liters] |
8.84
(49)
|
7.98
(29)
|
11.33
(36)
|
| Title | Terminal Elimination Half-Life (t1/2) |
|---|---|
| Description | Terminal elimination half-life following subcutaneous administration. |
| Time Frame | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 24 | 25 | 25 |
| Mean (Standard Deviation) [days] |
7.27
(1.09)
|
7.40
(1.03)
|
8.53
(1.61)
|
| Title | Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value |
|---|---|
| Description | Maximum LDL-C response using absolute on trial LDL-C data |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic (PD) analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Mean (Standard Deviation) [mg/dL] |
72.20
(20.185)
|
75.32
(31.964)
|
74.40
(25.290)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 97.35 | |
| Confidence Interval |
(2-Sided) 90% 84.659 to 111.943 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 103.96 | |
| Confidence Interval |
(2-Sided) 90% 90.405 to 119.557 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Emax: Change From Baseline |
|---|---|
| Description | LDL-C Emax expressed as change from baseline. |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Mean (Standard Deviation) [mg/dL] |
-96.88
(19.356)
|
-97.62
(26.967)
|
-90.46
(25.441)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 97.10 | |
| Confidence Interval |
(2-Sided) 90% 86.558 to 108.926 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 93.52 | |
| Confidence Interval |
(2-Sided) 90% 83.359 to 104.912 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Emax: Percent Change From Baseline |
|---|---|
| Description | LDL-C Emax expressed as percent change from baseline. |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Mean (Standard Deviation) [percent change] |
-57.47
(9.084)
|
-56.98
(14.740)
|
-54.96
(13.269)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 97.10 | |
| Confidence Interval |
(2-Sided) 90% 86.558 to 108.926 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 93.52 | |
| Confidence Interval |
(2-Sided) 90% 83.359 to 104.912 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) |
|---|---|
| Description | Time to LDL-C Emax |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Median (Full Range) [days] |
20.96
(7.461)
|
20.06
(5.173)
|
14.01
(7.102)
|
| Title | Area Under the LDL-C Effect Curve (AUEC): Absolute Value |
|---|---|
| Description | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 24 | 25 |
| Mean (Standard Deviation) [mg*day/dL] |
11181.64
(1545.335)
|
11682.39
(2063.772)
|
11231.39
(1928.904)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 102.51 | |
| Confidence Interval |
(2-Sided) 90% 97.555 to 107.717 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 102.02 | |
| Confidence Interval |
(2-Sided) 90% 97.131 to 107.151 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AUEC: Change From Baseline |
|---|---|
| Description | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed as change from baseline |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 24 | 25 |
| Mean (Standard Deviation) [mg*day/dL] |
-2982.16
(1431.589)
|
-2701.99
(1432.539)
|
-2546.68
(977.934)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 79.09 | |
| Confidence Interval |
(2-Sided) 90% 60.883 to 102.735 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 91.15 | |
| Confidence Interval |
(2-Sided) 90% 70.269 to 118.248 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AUEC: Percent Change From Baseline |
|---|---|
| Description | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline. |
| Time Frame | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 24 | 25 |
| Mean (Standard Deviation) [percent change] |
-1715.22
(758.720)
|
-1538.85
(724.925)
|
-1550.73
(583.745)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Thigh |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 79.09 | |
| Confidence Interval |
(2-Sided) 90% 60.883 to 102.735 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Bococizumab 150 mg Abdomen, Bococizumab 150 mg Upper Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | Ratios (and 90% confidence intervals) were expressed as percentages. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Means Ratio (%) |
| Estimated Value | 91.15 | |
| Confidence Interval |
(2-Sided) 90% 70.269 to 118.248 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Injection Site Reactions (ISRs) by Severity |
|---|---|
| Description | Acute injection site reactions (e.g, pain, pruritus, induration) were captured as adverse events (AEs). Intensity of the AE was described as mild (does not interfere with usual function), moderate (interferes to some extent with usual function), or severe (interferes significantly with participant's usual function). |
| Time Frame | Day 1 to Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Mild: injection site erythema |
1
4%
|
0
0%
|
2
8%
|
| Mild: injection site indurations |
1
4%
|
2
8%
|
0
0%
|
| Mild: injection site pain |
1
4%
|
0
0%
|
0
0%
|
| Mild: injection site pruritus |
0
0%
|
0
0%
|
1
4%
|
| Mild: injection site reaction |
1
4%
|
3
12%
|
1
4%
|
| Mild: injection site swelling |
0
0%
|
1
4%
|
0
0%
|
| Moderate: injection site erythema |
0
0%
|
0
0%
|
0
0%
|
| Moderate: injection site indurations |
0
0%
|
0
0%
|
0
0%
|
| Moderate: injection site pain |
0
0%
|
0
0%
|
0
0%
|
| Moderate: injection site pruritus |
0
0%
|
0
0%
|
0
0%
|
| Moderate: injection site reaction |
0
0%
|
0
0%
|
0
0%
|
| Moderate: injection site swelling |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site erythema |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site indurations |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site pain |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site pruritus |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site reaction |
0
0%
|
0
0%
|
0
0%
|
| Severe: injection site swelling |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) |
|---|---|
| Description | A participant is ADA positive if ADA titer (log2) >=6.23. A participant is nAb positive if nAb titer (log2) >=4.32. |
| Time Frame | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Positive ADA |
6
24%
|
6
24%
|
11
44%
|
| Positive nAb |
2
8%
|
2
8%
|
0
0%
|
| Title | Anti-Drug Antibody (ADA) Titer |
|---|---|
| Description | ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint. |
| Time Frame | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population included all participants who received at least 1 dose of study medication. Only confirmed ADA positive samples were analyzed for titer. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm |
|---|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. |
| Measure Participants | 25 | 25 | 25 |
| Day 15 |
NA
|
NA
|
|
| Day 29 |
NA
|
NA
|
|
| Day 57 |
NA
|
7.64
|
8.25
|
| Day 85 |
7.46
|
7.20
|
7.60
|
| Title | Neutralizing Antibody (nAb) Titer |
|---|---|
| Description | nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint. |
| Time Frame | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis population included all participants who received at least 1 dose of study medication. Only confirmed ADA positive samples were analyzed for nAb. nAb titer was determined if a sample is screened positive for nAb. nAb titer data for the Bococizumab 150 mg Upper Arm group is not presented as there were no nAb positive subjects. |
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh |
|---|---|---|
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. |
| Measure Participants | 25 | 25 |
| Day 29 |
NA
|
|
| Day 57 |
NA
|
NA
|
| Day 85 |
NA
|
NA
|
Adverse Events
| Time Frame | Baseline up to Day 85 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. | |||||
| Arm/Group Title | Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm | |||
| Arm/Group Description | Participants received a single dose of bococizumab 150 mg SC to the abdomen. | Participants received a single dose of bococizumab 150 mg SC to the thigh. | Participants received a single dose of bococizumab 150 mg SC to the upper arm. | |||
All Cause Mortality |
||||||
| Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Gastrointestinal disorders | ||||||
| Colitis ischaemic | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Bococizumab 150 mg Abdomen | Bococizumab 150 mg Thigh | Bococizumab 150 mg Upper Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/25 (52%) | 15/25 (60%) | 12/25 (48%) | |||
| Blood and lymphatic system disorders | ||||||
| Abdominal lymphadenopathy | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Eye disorders | ||||||
| Noninfective conjunctivitis | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Diarrhoea | 0/25 (0%) | 1/25 (4%) | 1/25 (4%) | |||
| Food poisoning | 1/25 (4%) | 0/25 (0%) | 0/25 (0%) | |||
| Frequent bowel movements | 0/25 (0%) | 1/25 (4%) | 1/25 (4%) | |||
| Nausea | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Oesophagitis | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Tongue dry | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Toothache | 1/25 (4%) | 0/25 (0%) | 1/25 (4%) | |||
| Umbilical hernia | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| General disorders | ||||||
| Fatigue | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Injection site erythema | 1/25 (4%) | 0/25 (0%) | 2/25 (8%) | |||
| Injection site induration | 1/25 (4%) | 2/25 (8%) | 0/25 (0%) | |||
| Injection site pain | 1/25 (4%) | 0/25 (0%) | 0/25 (0%) | |||
| Injection site pruritus | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Injection site reaction | 1/25 (4%) | 3/25 (12%) | 1/25 (4%) | |||
| Injection site swelling | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Therapeutic response changed | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Infections and infestations | ||||||
| Diverticulitis | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Gastroenteritis | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Infected dermal cyst | 1/25 (4%) | 0/25 (0%) | 0/25 (0%) | |||
| Tonsillitis | 1/25 (4%) | 0/25 (0%) | 0/25 (0%) | |||
| Tooth abscess | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Upper respiratory tract infection | 2/25 (8%) | 4/25 (16%) | 1/25 (4%) | |||
| Urinary tract infection | 0/25 (0%) | 2/25 (8%) | 0/25 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/25 (0%) | 1/25 (4%) | 1/25 (4%) | |||
| Back pain | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Pain in extremity | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/25 (4%) | 0/25 (0%) | 0/25 (0%) | |||
| Headache | 2/25 (8%) | 2/25 (8%) | 1/25 (4%) | |||
| Presyncope | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Sinus headache | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/25 (0%) | 0/25 (0%) | 1/25 (4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory tract congestion | 0/25 (0%) | 1/25 (4%) | 0/25 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Ecchymosis | 2/25 (8%) | 1/25 (4%) | 0/25 (0%) | |||
| Rash | 2/25 (8%) | 0/25 (0%) | 1/25 (4%) | |||
| Vascular disorders | ||||||
| Haematoma | 1/25 (4%) | 0/25 (0%) | 0/25 (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:
NCT02043301
Other Study ID Numbers:
- B1481024
First Posted:
Jan 23, 2014
Last Update Posted:
May 31, 2019
Last Verified:
Feb 1, 2019