To Assess Safety, Tolerability and Pharmacodynamics of Intravenous MEDI8111 After Single Ascending Doses.
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01958645
Collaborator
(none)
157
1
2
11
14.3
Study Details
Study Description
Brief Summary
A study to investigate the safety, tolerability and pharmacodynamics of MEDI8111 after single ascending doses in healthy male.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
A phase I, single-blind, randomised, placebo-controlled, single centre study to investigate the safety, tolerability and pharmacodynamics of intravenous MEDI8111 after single ascending doses in healthy male subjects.
Study Design
Study Type:
Interventional
Actual Enrollment
:
157 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Basic Science
Official Title:
A Phase I, Single-blind, Randomised, Placebo-controlled, Single Centre Study to Investigate the Safety, Tolerability and Pharmacodynamics of Intravenous MEDI8111 After Single Ascending Doses in Healthy Male Subjects
Study Start Date
:
Nov 1, 2013
Actual Primary Completion Date
:
Oct 1, 2014
Actual Study Completion Date
:
Oct 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A MEDI8111 |
Drug: MEDI8111
MEDI8111 lyophilisate for solution for infusion
|
| Placebo Comparator: B Placebo for MEDI8111 |
Other: Placebo
Placebo for MEDI8111 saline solution for infusion
|
Outcome Measures
Primary Outcome Measures
- Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination [From screening and up to the lab follow-up visit (Day 29)]
Secondary Outcome Measures
- Change From Baseline Endogenous Thrombin Potential (ETP) [Predose and Days 1-5]
For the baseline variables and adverse events the two placebo arms (placebo dose 1 and placebo dose 2) are recorded as one. For the secondary outcome measures the two placebo arms are recorded separately.
- Change From Baseline Factor II Concentrations by ECL Assay [Predose and 1-8 hours]
- Change From Baseline Factor II Concentrations by Clot Assay [Predose and 1-8 hours]
- Change From Baseline D-dimer Concentration [predose and 1-8 hours]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 40 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
- Provision of signed and dated, written informed consent prior to any study specific procedures, Healthy male subjects aged 18-40 years with suitable veins for cannulation or repeated venepuncture, Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weight at least 50 kg an no more than 100 kg inclusive, Male subjects should be willing to avoid fathering a child by either true abstinence or the use of two effective means of contraception from the day of dosing until 3 months after dosing with the IP. They should also be willing to use barrier methods from the day of dosing until 3 months after dosing.
Exclusion Criteria:
- Prothrombotic mutation such as factor V Leiden, or deficiencies of protein C, protein S, prothrombin, antithrombin or APC, Antibodies to coagulation FII, History or family history of venous or arterial thromboembolic event, and/or myocardial infarction before age of 50 years, ETP level at baseline >2000nM/min, FII level (by clot) at screening and/or at baseline outside 50-250% of the normal range
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | London | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Karin Wahlander, MD, AstraZeneca Mölndal, Sweden
- Study Chair: Anders Berggren, MD, AstraZeneca Mölndal, Sweden
- Principal Investigator: Timothy Mant, Prof, Quintiles London, United Kingdom
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01958645
Other Study ID Numbers:
- D5050C00001
First Posted:
Oct 9, 2013
Last Update Posted:
Feb 4, 2016
Last Verified:
Dec 1, 2015
Keywords provided by AstraZeneca
Study Results
Participant Flow
| Recruitment Details | Male healthy volunteers recruited by advertisement during the period October 2013 - October 2014 |
|---|---|
| Pre-assignment Detail | The study was prematurely terminated after 2 cohorts as dose escalation stopping criteria (PD thresholds) were reached and it was judged to be of limited value to expose more healthy subjects. Cohort 1: 2 placebo + 4 MEDI8111 dose 1. Cohort 2: 2 placebo + 4 MEDI8111 dose 2. |
| Arm/Group Title | Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 |
|---|---|---|---|
| Arm/Group Description | Placebo (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) |
| Period Title: Overall Study | |||
| STARTED | 4 | 4 | 4 |
| COMPLETED | 4 | 4 | 4 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Total |
|---|---|---|---|---|
| Arm/Group Description | Placebo (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | Total of all reporting groups |
| Overall Participants | 4 | 4 | 4 | 12 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
25
(9)
|
30
(6)
|
30
(6)
|
29
(7)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
4
100%
|
4
100%
|
4
100%
|
12
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
4
100%
|
4
100%
|
4
100%
|
12
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
25%
|
1
8.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
50%
|
1
25%
|
0
0%
|
3
25%
|
| White |
2
50%
|
3
75%
|
3
75%
|
8
66.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination |
|---|---|
| Description | |
| Time Frame | From screening and up to the lab follow-up visit (Day 29) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 |
|---|---|---|---|
| Arm/Group Description | Placebo (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) |
| Measure Participants | 4 | 4 | 4 |
| Subjects with any AE |
2
50%
|
3
75%
|
2
50%
|
| Gastrointestinal disorders |
1
25%
|
1
25%
|
1
25%
|
| Infections and infestations |
0
0%
|
1
25%
|
1
25%
|
| Investigations |
0
0%
|
1
25%
|
0
0%
|
| Musculoskeletal and connective tissue disorders |
0
0%
|
1
25%
|
0
0%
|
| Nervous system disorder |
0
0%
|
1
25%
|
0
0%
|
| Respiratory, thoracic and mediastinal disorders |
1
25%
|
0
0%
|
1
25%
|
| Skin and subcutaneous tissue disorders |
1
25%
|
0
0%
|
0
0%
|
| Title | Change From Baseline Endogenous Thrombin Potential (ETP) |
|---|---|
| Description | For the baseline variables and adverse events the two placebo arms (placebo dose 1 and placebo dose 2) are recorded as one. For the secondary outcome measures the two placebo arms are recorded separately. |
| Time Frame | Predose and Days 1-5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo Dose 1 | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Placebo Dose 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo dose 1 (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | Placebo dose 2 (Saline solution for infusion) |
| Measure Participants | 2 | 4 | 4 | 2 |
| 0.98 h |
16
(143)
|
131
(219)
|
NA
(NA)
|
NA
(NA)
|
| 1.03 h |
30.5
(138)
|
145
(263)
|
39.8
(72.1)
|
-35.0
(214)
|
| 1.25 h |
67.0
(356)
|
135
(345)
|
211
(179)
|
27.0
(80.6)
|
| 1.5 h |
166
(75)
|
-17.3
(120)
|
NA
(NA)
|
NA
(NA)
|
| 2 h |
32.5
(148)
|
178
(336)
|
147
(167)
|
-79.5
(95.5)
|
| 3 h |
57.0
(238)
|
188
(385)
|
NA
(NA)
|
NA
(NA)
|
| 4 h |
-88.0
(226)
|
72.8
(545)
|
157
(277)
|
4.50
(48.8)
|
| 8 h |
157
(161)
|
141
(288)
|
83.0
(216)
|
6.50
(33.2)
|
| 12 h |
82.5
(70.0)
|
366
(396)
|
NA
(NA)
|
NA
(NA)
|
| 24 h |
-29.0
(279)
|
115
(336)
|
86.0
(120)
|
70.5
(14.8)
|
| 36 h |
-59.0
(134)
|
329
(496)
|
NA
(NA)
|
NA
(NA)
|
| 48 h |
29.0
(222)
|
172
(264)
|
206
(261)
|
91.0
(26.9)
|
| 72 h |
183
(222)
|
71.5
(274)
|
139
(194)
|
73.5
(9.19)
|
| 96 h |
-95.0
(209)
|
-1.00
(483)
|
64.8
(223)
|
46.0
(8.49)
|
| Follow up |
-12.5
(13.4)
|
-34.5
(206)
|
NA
(NA)
|
NA
(NA)
|
| Title | Change From Baseline Factor II Concentrations by ECL Assay |
|---|---|
| Description | |
| Time Frame | Predose and 1-8 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo Dose 1 | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Placebo Dose 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo dose 1 (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | Placebo dose 2 (Saline solution for infusion) |
| Measure Participants | 2 | 4 | 4 | 2 |
| 0.33 h |
-0.0810
(0.0410)
|
-0.0188
(0.0661)
|
NA
(NA)
|
NA
(NA)
|
| 0.67 h |
-0.0480
(0.0113)
|
0.0275
(0.0377)
|
NA
(NA)
|
NA
(NA)
|
| 0.98 h |
-0.134
(0.0368)
|
0.00450
(0.0896)
|
NA
(NA)
|
NA
(NA)
|
| 1 h |
-0.131
(0.0156)
|
-0.0305
(0.0435)
|
0.166
(0.0632)
|
0.0650
(0.0212)
|
| 1.25 h |
-0.143
(0.00354)
|
-0.0920
(0.0881)
|
0.116
(0.113)
|
0.0600
(0.0424)
|
| 1.5 h |
-0.132
(0.121)
|
-0.124
(0.148)
|
NA
(NA)
|
NA
(NA)
|
| 2 h |
-0.0655
(0.0629)
|
0.00450
(0.188)
|
0.111
(0.129)
|
0.0800
(0.0849)
|
| 3 h |
-0.0675
(0.248)
|
0.0608
(0.120)
|
NA
(NA)
|
NA
(NA)
|
| 4 h |
-0.127
(0.279)
|
0.123
(0.0663)
|
0.141
(0.155)
|
0.0450
(0.0495)
|
| 8 h |
0.00650
(0.122)
|
0.0633
(0.0801)
|
0.0835
(0.0731)
|
-0.00900
(0.0410)
|
| Title | Change From Baseline Factor II Concentrations by Clot Assay |
|---|---|
| Description | |
| Time Frame | Predose and 1-8 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo Dose 1 | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Placebo Dose 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo dose 1 (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | Placebo dose 2 (Saline solution for infusion) |
| Measure Participants | 2 | 4 | 4 | 2 |
| 0.33 h |
7.65
(26.4)
|
-1.40
(7.67)
|
NA
(NA)
|
NA
(NA)
|
| 0.67 h |
3.15
(17.2)
|
1.35
(6.95)
|
NA
(NA)
|
NA
(NA)
|
| 0.98 h |
-9.35
(12.2)
|
-2.40
(4.25)
|
NA
(NA)
|
NA
(NA)
|
| 1 h |
-14.4
(13.6)
|
-1.15
(4.22)
|
13.7
(14.5)
|
7.30
(0.00)
|
| 1.25 |
-6.85
(18.6)
|
-0.400
(5.54)
|
12.2
(9.55)
|
8.30
(1.41)
|
| 1.5 h |
-10.9
(12.9)
|
-0.400
(8.67)
|
NA
(NA)
|
NA
(NA)
|
| 2 h |
-8.85
(8.70)
|
0.350
(5.45)
|
10.5
(7.84)
|
2.80
(4.95)
|
| 3 h |
-5.85
(12.9)
|
1.10
(9.73)
|
NA
(NA)
|
NA
(NA)
|
| 4 h |
0.150
(15.8)
|
2.10
(4.45)
|
18.2
(9.02)
|
7.30
(4.24)
|
| 8 h |
-9.85
(10.1)
|
-1.90
(5.78)
|
11.7
(9.12)
|
9.30
(4.24)
|
| Title | Change From Baseline D-dimer Concentration |
|---|---|
| Description | |
| Time Frame | predose and 1-8 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo Dose 1 | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Placebo Dose 2 |
|---|---|---|---|---|
| Arm/Group Description | Placebo dose 1 (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | Placebo dose 2 (Saline solution for infusion) |
| Measure Participants | 2 | 4 | 4 | 2 |
| 0.98 h |
-0.0169
(0.0144)
|
0.0408
(0.103)
|
NA
(NA)
|
NA
(NA)
|
| 1.03 h |
0.0432
(0.0564)
|
0.0383
(0.109)
|
0.0108
(0.0190)
|
0.0270
(0.0141)
|
| 1.25 h |
0.0232
(0.113)
|
0.000750
(0.0336)
|
0.0333
(0.0306)
|
0.0170
(0.0566)
|
| 1.5 h |
-0.00185
(0.0214)
|
0.408
(0.795)
|
NA
(NA)
|
NA
(NA)
|
| 2 h |
0.0682
(0.135)
|
0.0382
(0.0813)
|
0.0610
(0.0760)
|
0.0170
(0.0424)
|
| 3 h |
0.0732
(0.0846)
|
0.00325
(0.0237)
|
NA
(NA)
|
NA
(NA)
|
| 4 h |
NA
(NA)
|
NA
(NA)
|
0.0933
(0.0810)
|
0.207
(0.0849)
|
| 8 h |
0.588
(0.799)
|
0.0858
(0.0914)
|
0.0633
(0.0630)
|
0.0470
(0.0849)
|
Adverse Events
| Time Frame | At screening, Days 1-5 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | |||
| Arm/Group Description | Placebo (Saline solution for infusion) | MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | |||
All Cause Mortality |
||||||
| Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 3/4 (75%) | 2/4 (50%) | |||
| Gastrointestinal disorders | ||||||
| Gastrooesophageal reflux disease | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | |||
| Hypoaesthesia oral | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | |||
| Gastritis | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | |||
| Infections and infestations | ||||||
| Gastroenteritis | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | |||
| Upper respiratory tract infection | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | |||
| Investigations | ||||||
| Fibrin D-dimer increased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscle spasms | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | |||
| Nervous system disorders | ||||||
| Muscle contractions involuntary | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Increased upper airway secretion | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | |||
| Nasal congestion | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis contact | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | |||
Limitations/Caveats
Limitations: few subjects, high variability of coagulation variables
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Anders Berggren, MD, PhD |
|---|---|
| Organization | AstraZeneca |
| Phone | |
| clinicaltrialtransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01958645
Other Study ID Numbers:
- D5050C00001
First Posted:
Oct 9, 2013
Last Update Posted:
Feb 4, 2016
Last Verified:
Dec 1, 2015