Safety And Tolerability Study Of RN6G In Patients With Dry, Age-Related Macular Degeneration
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00877032
Collaborator
(none)
57
20
1
27
2.9
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety and tolerability of RN6G in patients with dry, age-related macular degeneration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
57 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase I, Double-masked, Placebo-controlled Study Evaluating The Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Immunogenicity Of Single Escalating Doses Of Rn6g In Patients With Dry, Age-related Macular Degeneration (Amd)
Study Start Date
:
Apr 1, 2009
Actual Primary Completion Date
:
Jul 1, 2011
Actual Study Completion Date
:
Jul 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1
|
Biological: RN6G
intravenous, single dose, dose ranging from 0.3mg/kg up to a maximum of 40 mg/kg.
Biological: Placebo
intravenous, single dose with experimental dose.
|
Outcome Measures
Primary Outcome Measures
- Incidence and Severity of Ocular Adverse Events (AEs) [Baseline up to Day 168]
AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Ocular AE was identified by spontaneous report or ocular examination: early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA); low-luminance BCVA; pupillary light response, extra-ocular muscle movements, external examination of the eyelids and eyelashes, slit-lamp biomicroscopic examination (SLE) of all components of the anterior and posterior segments, intra-ocular pressure (IOP), and dilated ocular fundus examination of the vitreous and retina. AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with ocular (related to eye) AEs and severity was reported.
- Incidence and Severity of Systemic Adverse Events (AEs) [Baseline up to Day 168]
AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Systemic AEs was identified by spontaneous report or physical and neurological examinations changes in vital signs, clinical laboratory abnormalities, 12-lead electrocardiograms (ECG), brain magnetic resonance imaging (MRI). AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with systemic (all AEs including eye-related) AEs and severity was reported.
Secondary Outcome Measures
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Participants who received RN6G were reported.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received RN6G were reported.
- Maximum Observed Plasma Concentration (Cmax) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
Participants who received RN6G were reported.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
Participants who received RN6G were reported.
- Volume of Distribution (Vd) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Participants who received RN6G were reported and volume was measured as volume/kg of body weight.
- Clearance (CL) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received RN6G were reported and clearance was measured as mL/hr/kg of body weight.
- Mean Residence Time (MRT) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
MRT was calculated as area under the moment curve from time 0 to extrapolated infinite time (AUMC[0 to inf])/area under the concentration effect curve from time 0 to extrapolated infinite time (AUC[0 to inf]). AUMC (0 to inf)= area under the moment curve from 0 to time t (AUMC 0-t) + [(Ct*tlast )/lamdaz ] + [Ct/(lamdaz )^2 ] where Ct= last measurable concentration, tlast= last measurable time, lamdaz= apparent terminal elimination rate constant. Participants who received RN6G were reported.
- Plasma Terminal Half-life (t1/2) of RN6G [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. Participants who received RN6G were reported.
- Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168]
- Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) [Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165]
AUC (0-165d)= Area under the plasma concentration versus time curve from time zero (pre-dose) to Day 165.
- Number of Participants With Anti-Drug Anti-body [Baseline up to Day 168]
Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Be of non-childbearing potential.
-
Diagnosis of dry AMD as defined by the Age-Related Eye Disease Study (AREDS, 2005), including uni- or multi-focal GA, without foveal involvement.
-
BCVA of 20/320 or better in the worst eye.
Exclusion Criteria:
-
Diagnosis of exudative (wet) AMD, with subretinal or choroidal neovascular lesions.
-
Diagnosis or history of Alzheimer's disease, dementia or neurodegenerative disorders.
-
Diagnosis or recent history of clinically significant cerebrovascular disease.
-
Uncontrolled hypertension.
-
Uncontrolled Type 1 or Type 2 diabetes mellitus.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dedicated Phase 1 | Phoenix | Arizona | United States | 85013 |
| 2 | Retinal Consultants of AZ | Phoenix | Arizona | United States | 85014 |
| 3 | Insight Diagnostic Imaging Center | Phoenix | Arizona | United States | 85015 |
| 4 | Amir Hedayati-Rad, MD | Glendale | California | United States | 91206 |
| 5 | United Medical Imaging | Inglewood | California | United States | 90301 |
| 6 | United Medical Research Institute | Inglewood | California | United States | 90301 |
| 7 | California Pharmacy and Compounding Center | Newport Beach | California | United States | 92660 |
| 8 | Jasper Clinic, Inc. | Kalamazoo | Michigan | United States | 49007 |
| 9 | Jonathan Rowe, MD | Kalamazoo | Michigan | United States | 49048 |
| 10 | Ronald VanderLugt, MD | Kalamazoo | Michigan | United States | 49048 |
| 11 | CEDRA Clinical Research, LLC | San Antonio | Texas | United States | 78217 |
| 12 | Village Drive Imaging Center | San Antonio | Texas | United States | 78217 |
| 13 | Specialty MRI | San Antonio | Texas | United States | 78229 |
| 14 | Medical Center Ophthalmology Associates | San Antonio | Texas | United States | 78233 |
| 15 | Medical Center Ophthalmology Associates | San Antonio | Texas | United States | 78240 |
| 16 | Retinal Consultants of San Antonio | San Antonio | Texas | United States | 78240 |
| 17 | EZ Pass Rx | Bountiful | Utah | United States | 84010 |
| 18 | Lifetree Clinical Research | Salt Lake City | Utah | United States | 84106 |
| 19 | Rocky Mountain Eye Care Associates, LC | Salt Lake City | Utah | United States | 84107 |
| 20 | Western Neurological Associates | Salt Lake City | Utah | United States | 84124 |
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:
NCT00877032
Other Study ID Numbers:
- B1181001
First Posted:
Apr 7, 2009
Last Update Posted:
Mar 31, 2015
Last Verified:
Mar 1, 2015
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | From a given cohort, no more than 3 participants received treatment on Day 1, the remaining participants in the respective cohort received treatment at least 24 hours thereafter. All the remaining participants were treated on same day, if required, as per site scheduling. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Period Title: Overall Study | |||||||
| STARTED | 6 | 6 | 6 | 7 | 6 | 6 | 20 |
| Treated | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| COMPLETED | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 | 54 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
68.2
(11.1)
|
70.2
(9.9)
|
65.5
(10.4)
|
69.2
(3.7)
|
67.8
(7.5)
|
65.0
(6.5)
|
67.4
(8.2)
|
67.6
(8.1)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
4
66.7%
|
2
33.3%
|
5
83.3%
|
2
33.3%
|
5
83.3%
|
4
66.7%
|
14
77.8%
|
36
66.7%
|
| Male |
2
33.3%
|
4
66.7%
|
1
16.7%
|
4
66.7%
|
1
16.7%
|
2
33.3%
|
4
22.2%
|
18
33.3%
|
Outcome Measures
| Title | Incidence and Severity of Ocular Adverse Events (AEs) |
|---|---|
| Description | AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Ocular AE was identified by spontaneous report or ocular examination: early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA); low-luminance BCVA; pupillary light response, extra-ocular muscle movements, external examination of the eyelids and eyelashes, slit-lamp biomicroscopic examination (SLE) of all components of the anterior and posterior segments, intra-ocular pressure (IOP), and dilated ocular fundus examination of the vitreous and retina. AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with ocular (related to eye) AEs and severity was reported. |
| Time Frame | Baseline up to Day 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Ocular AEs |
1
16.7%
|
3
50%
|
2
33.3%
|
1
16.7%
|
4
66.7%
|
3
50%
|
6
33.3%
|
| Mild ocular AEs: right eye |
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
1
16.7%
|
0
0%
|
2
11.1%
|
| Mild ocular AEs: left eye |
1
16.7%
|
2
33.3%
|
1
16.7%
|
0
0%
|
1
16.7%
|
2
33.3%
|
2
11.1%
|
| Mild ocular AEs: both eyes |
0
0%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
3
16.7%
|
| Moderate ocular AEs: right eye |
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
1
16.7%
|
0
0%
|
1
5.6%
|
| Moderate ocular AEs: left eye |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
2
33.3%
|
0
0%
|
1
5.6%
|
| Moderate ocular AEs: both eyes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Severe ocular AEs: right eye |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Severe ocular AEs: left eye |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Severe ocular AEs: both eyes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Incidence and Severity of Systemic Adverse Events (AEs) |
|---|---|
| Description | AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Systemic AEs was identified by spontaneous report or physical and neurological examinations changes in vital signs, clinical laboratory abnormalities, 12-lead electrocardiograms (ECG), brain magnetic resonance imaging (MRI). AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with systemic (all AEs including eye-related) AEs and severity was reported. |
| Time Frame | Baseline up to Day 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Systemic AEs |
4
66.7%
|
5
83.3%
|
5
83.3%
|
4
66.7%
|
6
100%
|
6
100%
|
15
83.3%
|
| Mild systemic AEs |
4
66.7%
|
5
83.3%
|
5
83.3%
|
2
33.3%
|
6
100%
|
5
83.3%
|
15
83.3%
|
| Moderate systemic AEs |
1
16.7%
|
2
33.3%
|
2
33.3%
|
2
33.3%
|
3
50%
|
2
33.3%
|
7
38.9%
|
| Severe systemic AEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G |
|---|---|
| Description | AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis population included all participants who received any amount of the single dose of RN6G. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [microgram*hour/milliliter (mcg*hr/mL)] |
1003
(399)
|
4516
(627)
|
19591
(3657)
|
76987
(18255)
|
163049
(57995)
|
486191
(64822)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G |
|---|---|
| Description | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [mcg*hr/mL] |
836
(326)
|
3990
(593)
|
17878
(3395)
|
72792
(15929)
|
155377
(52319)
|
472239
(59181)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of RN6G |
|---|---|
| Description | Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [mcg/mL] |
4.70
(0.87)
|
23.1
(2.9)
|
75.2
(9.3)
|
286
(58)
|
435
(87)
|
1245
(142)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G |
|---|---|
| Description | Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 |
| Median (Full Range) [hours] |
2.1
|
2.1
|
2.0
|
4.5
|
2.5
|
2.1
|
| Title | Volume of Distribution (Vd) of RN6G |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Participants who received RN6G were reported and volume was measured as volume/kg of body weight. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [mL/kilogram (mL/kg)] |
384
(86.8)
|
555
(180)
|
336
(74.8)
|
230
(39.5)
|
198
(57.1)
|
98.0
(12.1)
|
| Title | Clearance (CL) of RN6G |
|---|---|
| Description | CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received RN6G were reported and clearance was measured as mL/hr/kg of body weight. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [mL/hr/kg] |
0.336
(0.117)
|
0.225
(0.0287)
|
0.158
(0.031)
|
0.137
(0.037)
|
0.134
(0.040)
|
0.0835
(0.0115)
|
| Title | Mean Residence Time (MRT) of RN6G |
|---|---|
| Description | MRT was calculated as area under the moment curve from time 0 to extrapolated infinite time (AUMC[0 to inf])/area under the concentration effect curve from time 0 to extrapolated infinite time (AUC[0 to inf]). AUMC (0 to inf)= area under the moment curve from 0 to time t (AUMC 0-t) + [(Ct*tlast )/lamdaz ] + [Ct/(lamdaz )^2 ] where Ct= last measurable concentration, tlast= last measurable time, lamdaz= apparent terminal elimination rate constant. Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [days] |
36.2
(19.7)
|
57.3
(16.8)
|
51.5
(5.8)
|
37.7
(8.3)
|
41.9
(10.0)
|
38.0
(6.8)
|
| Title | Plasma Terminal Half-life (t1/2) of RN6G |
|---|---|
| Description | Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. Participants who received RN6G were reported. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included all participants who received any amount of the single dose of RN6G. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [days] |
37.5
(20.1)
|
71.5
(20.5)
|
61.4
(5.8)
|
50.1
(9.4)
|
43.3
(6.7)
|
34.2
(5.1)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) |
|---|---|
| Description | |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Mean (Standard Deviation) [picogram/milliliter (pg/mL)] |
3607
(1517)
|
10318
(3312)
|
21267
(2836)
|
59000
(14599)
|
70967
(10265)
|
75700
(11773)
|
533
(177)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) |
|---|---|
| Description | |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Median (Full Range) [hours] |
14.3
|
26.0
|
26.1
|
160
|
317
|
402
|
14.3
|
| Title | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) |
|---|---|
| Description | AUC (0-165d)= Area under the plasma concentration versus time curve from time zero (pre-dose) to Day 165. |
| Time Frame | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Mean (Standard Deviation) [nanogram*hr/mL (ng*hr/mL)] |
2512
(752)
|
4512
(1780)
|
12041
(2553)
|
46852
(12562)
|
85441
(22829)
|
113547
(19280)
|
1572
(392)
|
| Title | Number of Participants With Anti-Drug Anti-body |
|---|---|
| Description | Participants tested positive for anti-drug anti-body on at least one or more occasions were reported. |
| Time Frame | Baseline up to Day 168 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo. |
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 |
| Number [participants] |
2
33.3%
|
1
16.7%
|
0
0%
|
2
33.3%
|
1
16.7%
|
2
33.3%
|
0
0%
|
Adverse Events
| Time Frame | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||||||||
| Arm/Group Title | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | |||||||
| Arm/Group Description | Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | Single intravenous infusion dose of placebo matched to RN6G on Day 1. | |||||||
All Cause Mortality |
||||||||||||||
| RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | ||||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | ||||||||
| 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 | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Carotid artery stenosis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | ||||||||
| 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 | 4/6 (66.7%) | 5/6 (83.3%) | 5/6 (83.3%) | 4/6 (66.7%) | 6/6 (100%) | 6/6 (100%) | 15/18 (83.3%) | |||||||
| Cardiac disorders | ||||||||||||||
| Atrial fibrillation | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Atrioventricular block first degree | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Sinus arrhythmia | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Supraventricular extrasystoles | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Tinnitus | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Vertigo | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Blepharitis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Cataract | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Cataract cortical | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 3/18 (16.7%) | |||||||
| Cataract nuclear | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Cataract subcapsular | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Conjunctival hyperaemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Iritis | 0/6 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Lacrimation increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Ocular icterus | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Pupillary disorder | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Retinal haemorrhage | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Retinal pigment epitheliopathy | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Visual acuity reduced | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Visual impairment | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Vitreous detachment | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Colonic polyp | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Diarrhoea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Diverticulum | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Nausea | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Vomiting | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Infusion site haematoma | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Injection site pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Pyrexia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Sensation of foreign body | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Swelling | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Vessel puncture site haemorrhage | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Infections and infestations | ||||||||||||||
| Bronchitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Cystitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Influenza | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Nasopharyngitis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Rash pustular | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Sinusitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Upper respiratory tract infection | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Urinary tract infection | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Vulvovaginal mycotic infection | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Back injury | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Contusion | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Excoriation | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Femur fracture | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Incision site pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Joint sprain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Limb injury | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Investigations | ||||||||||||||
| Aspartate aminotransferase increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Blood creatine phosphokinase increased | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Blood glucose increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Blood iron decreased | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Blood phosphorus increased | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Blood pressure diastolic decreased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Blood pressure increased | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Blood triglycerides increased | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Body temperature increased | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Visual acuity tests abnormal | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Weight decreased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Hypercholesterolaemia | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Arthritis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Back pain | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Costochondritis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Muscle spasms | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Musculoskeletal pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Neck pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Pain in extremity | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Basal cell carcinoma | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Cyst | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Nervous system disorders | ||||||||||||||
| Cognitive disorder | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Dizziness | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Headache | 1/6 (16.7%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 4/6 (66.7%) | 2/6 (33.3%) | 3/18 (16.7%) | |||||||
| Migraine with aura | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Paraesthesia oral | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Presyncope | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Sensory disturbance | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Abnormal dreams | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Anxiety | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Insomnia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Polyuria | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Benign prostatic hyperplasia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Oropharyngeal pain | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Wheezing | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/18 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dermatitis contact | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Dyshidrosis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Hyperhidrosis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/18 (5.6%) | |||||||
| Rash | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Skin laceration | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Contusion | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | |||||||
| Poor peripheral circulation | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/18 (0%) | |||||||
Limitations/Caveats
Results for pharmacodynamic parameters [Cmax, Tmax and AUC (0-65d) of A beta(1-X)], are presented as absolute values at specified time points and not as change from baseline as planned.
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:
NCT00877032
Other Study ID Numbers:
- B1181001
First Posted:
Apr 7, 2009
Last Update Posted:
Mar 31, 2015
Last Verified:
Mar 1, 2015