A Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease

A Phase 1, Single Ascending Dose Study to Evaluate the Safety of MEDI2338 in Subjects With Chronic Obstructive Pulmonary Disease

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01322594

Enrollment

Registered

2011-03-24

Start date

2011-03-31

Completion date

2011-12-31

Last updated

2013-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease, COPD

Brief summary

Phase I study to evaluate the safety and tolerability of single ascending intravenous doses of MEDI2338 in subjects with stable, mild to moderate chronic obstructive pulmonary disease (COPD).

Interventions

BIOLOGICALMEDI2338

MEDI2338 single intravenous (IV) dose (lowest dose)

OTHERPlacebo

Placebo single IV dose

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

* Aged ≥ 40 years at time of screening. * Females of non-childbearing potential defined as surgically sterile or at least 2 years postmenopausal. * Males, unless surgically sterile, must use 2 highly effective methods of birth control from screening through end of trial. * A diagnosis of mild to moderate COPD. * Cigarette smoking history of ≥10 pack years. * Ability to understand and comply with protocol requirements, instructions and restrictions. * COPD symptoms adequately controlled on a therapeutic regimen that has not changed in the 4 weeks prior to screening.

Exclusion criteria

* Current diagnosis of any respiratory condition other than COPD. * Active or history of any disease or condition that would, in the opinion of the investigator and/or medical monitor, place the subject at an unacceptable risk to participate in this study. * History of or suspected history of alcohol misuse or recreational substance abuse. * Treatment with oral or IV corticosteroids within 8 weeks prior to screening. * Concurrent enrolment in another clinical study. * Receipt of any investigational drug therapy of use of any biologicals within 6 months prior to screening. * Known history of allergy or reaction to any component of the investigational product.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Clinically Significant Serum Chemistry Laboratory Results	Days 1 - 92	Number of participants experiencing clinically significant serum chemistry laboratory results. A clinically significant serum chemistry laboratory result is defined as an abnormal serum chemistry laboratory result that results in a treatment-emergent adverse event.
Incidence of Adverse Events	Days 1 - 92	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Incidence of Serious Adverse Events	Days 1 - 92	Number of participants experiencing serious adverse events
Incidence of Clinically Significant Hematology Laboratory Results	Days 1 - 92	Number of participants experiencing clinically significant hematology laboratory results. A clinically significant hematology laboratory result is defined as an abnormal hematology laboratory result that results in a treatment-emergent adverse event.
Incidence of Clinically Significant Electrocardiogram Results	Days 1 - 92	Number of participants experiencing clinically significant electrocardiogram results. A clinically significant electrocardiogram result is defined as an abnormal electrocardiogram result that results in a treatment-emergent adverse event.
Incidence of Clinically Significant Vital Signs Results	Days 1 - 92	Number of participants experiencing clinically significant vital signs results. A clinically significant vital signs result is defined as an abnormal vital signs result that results in a treatment-emergent adverse event.

Secondary

Measure	Time frame	Description
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity	Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92)	Area under the serum concentration-time curve from time zerio to infinity of MEDI2338
Area Under the Serum Concentration-Time Profile From Time Zero to the Last Measurable Time Point	Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92)	Area under the serum concentration-time profile from time zero to the last measurable time point of MEDI2338
Incidence of Anti-drug Antibodies (ADA) to MEDI2338	Days 1, 57, and 92	Number of participants with ADA to MEDI2338
Observed Maximum Concentration (Cmax)	Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92)	Cmax of MEDI2338
Apparent Terminal Elimination Phase Half-life (t1/2)	Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92)	t1/2 of MEDI2338
Clearance (CL)	Pre-dose (Day 1) and post-dose (Days 1 [end of infusion, and 30 minutes and 1, 3, 8, and 24 hours postinfusion], 2, 3, 5, 8, 10, 15, 22, 29, 36, 43, 57, 71, and 92)	CL of MEDI2338

Countries

South Africa, United Kingdom

Participant flow

Recruitment details

A total of 31 participants provided written informed consent and participated in the study at 3 sites in South Africa (2 sites) and the United Kingdom (1 site) between 24Feb2011 and 25Nov2011.

Pre-assignment details

Eligibile participants in the 10 and 30 mg dose groups received MEDI2338 in an open-label manner. Eligible participants in the 100, 300, and 1000 dose groups were randomized in a 3:1 ratio to receive MEDI2338 or placebo.

Participants by arm

Arm	Count
Placebo Placebo administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump	6
MEDI2338 10 MG MEDI2338 (10 mg) administered as a single, fixed intravenous (IV) dose over a minimum of 60 minutes using an infusion pump	3
MEDI2338 30 MG MEDI2338 (30 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump	3
MEDI2338 100 MG MEDI2338 (100 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump	6
MEDI2338 300 MG MEDI2338 (300 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump	7
MEDI2338 1000 MG MEDI2338 (1000 mg) administered as a single, fixed IV dose over a minimum of 60 minutes using an infusion pump	6
Total	31

Baseline characteristics

Characteristic	Placebo	MEDI2338 10 MG	MEDI2338 30 MG	MEDI2338 100 MG	MEDI2338 300 MG	MEDI2338 1000 MG	Total
Age Continuous	61.3 Years STANDARD_DEVIATION 8	57.0 Years STANDARD_DEVIATION 4	59.7 Years STANDARD_DEVIATION 11	60.3 Years STANDARD_DEVIATION 7.1	55.1 Years STANDARD_DEVIATION 5.3	60.8 Years STANDARD_DEVIATION 6	59.1 Years STANDARD_DEVIATION 6.8
Sex: Female, Male Female	4 Participants	1 Participants	2 Participants	2 Participants	2 Participants	0 Participants	11 Participants
Sex: Female, Male Male	2 Participants	2 Participants	1 Participants	4 Participants	5 Participants	6 Participants	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 6	3 / 3	3 / 3	6 / 6	7 / 7	5 / 6
serious Total, serious adverse events	0 / 6	0 / 3	0 / 3	0 / 6	0 / 7	0 / 6

Outcome results

Primary

Incidence of Adverse Events

Number of participants experiencing adverse events (includes both adverse events and serious adverse events)

Time frame: Days 1 - 92