Trial Outcomes & Findings for To Assess the Safety, Tolerability, and Pharmacokinetics of AZD7624 in Healthy Volunteers and COPD Patients (NCT NCT01817855)

Results Overview

Summary of number of subjects who had at least one adverse event in any category (Safety analysis set)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

52 participants

Primary outcome timeframe

Up to 24 days

Results posted on

2016-03-30

Participant Flow

Both the lung deposited doses and total delivered doses are reported in clinical study report, and the conversion is: In cohort 1 to 6, the lung deposited doses 151 µg, 303 µg, 595 µg, 1191 µg, 1160 µg and 580 µg are equivalent to the delivered doses 261µg, 522µg, 1027µg, 2053µg, 1932µg and 966µg, respectively.

The screening period for all the subjects was from Day -42 to Day -2. Admission on day -1. A 8 to 9 days treatment period, 7 to 9 days follow up period. It was planned to enrol to 32 healthy volunteers and 20 COPD to the study, but 4 COPD patients (Due to stopping cohort 4 prematurly) and one healthy volunteer (in cohort 3) were not enrolled.

Participant milestones

Participant milestones
Measure	AZD7624 Healthy Volunteers Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD COPD Patients with Placebo, once daily
Overall Study STARTED	23	8	11	5
Overall Study COMPLETED	23	6	9	5
Overall Study NOT COMPLETED	0	2	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

To Assess the Safety, Tolerability, and Pharmacokinetics of AZD7624 in Healthy Volunteers and COPD Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD7624 Healthy Volunteers n=23 Participants Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=8 Participants Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=11 Participants COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=5 Participants COPD Patients with Placebo, once daily	Total n=47 Participants Total of all reporting groups
Age, Continuous	36 Years STANDARD_DEVIATION 9.7 • n=93 Participants	32 Years STANDARD_DEVIATION 9.1 • n=4 Participants	65 Years STANDARD_DEVIATION 9.7 • n=27 Participants	65 Years STANDARD_DEVIATION 8.7 • n=483 Participants	45.3 Years STANDARD_DEVIATION 17.1 • n=36 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	3 Participants n=36 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	8 Participants n=4 Participants	10 Participants n=27 Participants	3 Participants n=483 Participants	44 Participants n=36 Participants

PRIMARY outcome

Timeframe: Up to 24 days

Summary of number of subjects who had at least one adverse event in any category (Safety analysis set)

Outcome measures

Outcome measures
Measure	AZD7624 Healthy Volunteers n=23 Participants Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=8 Participants Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=11 Participants COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=5 Participants COPD Patients with Placebo, once daily	AZD7624 Healthy Volunteers Cohort 2 Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily	AZD7624 Healthy Volunteers Cohort 3 Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily
Adverse Events Any Adverse Event (AE)	6 Participants	3 Participants	7 Participants	2 Participants	—	—
Adverse Events Any AE with outcome = death	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Adverse Events Any SAE (including events with outcome = death)	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Adverse Events Any AE leading to discontinuation	0 Participants	1 Participants	2 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.

Population: PK analysis set

Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. \*AUC(0-tau) = AUC(0-last) where for cohorts 2,3,4,5 and 6 tau=24 hours and for cohort 1, tau=12 hours . Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.

Outcome measures

Outcome measures
Measure	AZD7624 Healthy Volunteers n=3 Participants Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=6 Participants Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=6 Participants COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=6 Participants COPD Patients with Placebo, once daily	AZD7624 Healthy Volunteers Cohort 2 n=6 Participants Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily	AZD7624 Healthy Volunteers Cohort 3 n=5 Participants Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily
Summary of Pharmacokinetic Parameters (AUC(0-tau) )	40.1 nmol*h/L Geometric Coefficient of Variation 11.4	27.4 nmol*h/L Geometric Coefficient of Variation 17.3	13.3 nmol*h/L Geometric Coefficient of Variation 50.4	3.88 nmol*h/L Geometric Coefficient of Variation 28.5	9.31 nmol*h/L Geometric Coefficient of Variation 12.7	15.2 nmol*h/L Geometric Coefficient of Variation 33.3

SECONDARY outcome

Timeframe: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.

Population: PK analysis set

Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.

Outcome measures

Outcome measures
Measure	AZD7624 Healthy Volunteers n=3 Participants Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=6 Participants Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=6 Participants COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=6 Participants COPD Patients with Placebo, once daily	AZD7624 Healthy Volunteers Cohort 2 n=6 Participants Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily	AZD7624 Healthy Volunteers Cohort 3 n=5 Participants Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily
Summary of Pharmacokinetic Parameters (Cmax)	11.9 nmol/L Geometric Coefficient of Variation 13.4	15.6 nmol/L Geometric Coefficient of Variation 38.3	3.08 nmol/L Geometric Coefficient of Variation 54.6	2.14 nmol/L Geometric Coefficient of Variation 49.5	6.23 nmol/L Geometric Coefficient of Variation 22.8	8.07 nmol/L Geometric Coefficient of Variation 39.5

SECONDARY outcome

Timeframe: PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3.

Population: PK analysis set

Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken.

Outcome measures

Outcome measures
Measure	AZD7624 Healthy Volunteers n=3 Participants Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=6 Participants Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=6 Participants COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=6 Participants COPD Patients with Placebo, once daily	AZD7624 Healthy Volunteers Cohort 2 n=6 Participants Healthy volunteers on Cohort 2 with 522 µg delivered dose of AZD7624, twice daily	AZD7624 Healthy Volunteers Cohort 3 n=5 Participants Healthy volunteers on Cohort 3 with 1027 µg delivered dose of AZD7624, twice daily
Summary of Pharmacokinetic Parameters (Cmin)	0.797 nmol/L Geometric Coefficient of Variation 22.2	0.602 nmol/L Geometric Coefficient of Variation 15.7	0.355 nmol/L Geometric Coefficient of Variation 47.3	0.183 nmol/L Geometric Coefficient of Variation 44.0	0.453 nmol/L Geometric Coefficient of Variation 18.6	0.719 nmol/L Geometric Coefficient of Variation 36.9

Adverse Events

AZD7624 Healthy Volunteers

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Healthy Volunteers

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AZD7624 COPD

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo COPD

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	AZD7624 Healthy Volunteers n=23 participants at risk Healthy Volunteers with 261 µg to 2053 µg delivered dose of AZD7624, once daily or twice daily	Placebo Healthy Volunteers n=8 participants at risk Healthy Volunteers with Placebo, once daily or twice daily	AZD7624 COPD n=11 participants at risk COPD patients with 966 µg or 1932 µg delivered dose of AZD7624, once daily	Placebo COPD n=5 participants at risk COPD Patients with Placebo, once daily
Respiratory, thoracic and mediastinal disorders Cough, Bronchospasm, Wheezing	17.4% 4/23 • Up to 24 days	12.5% 1/8 • Up to 24 days	9.1% 1/11 • Up to 24 days	0.00% 0/5 • Up to 24 days
Gastrointestinal disorders Mouth ulceration, Dry mouth, Nausea	4.3% 1/23 • Up to 24 days	25.0% 2/8 • Up to 24 days	9.1% 1/11 • Up to 24 days	0.00% 0/5 • Up to 24 days
General disorders Chest discomfort, Vessel puncture site bruise	4.3% 1/23 • Up to 24 days	25.0% 2/8 • Up to 24 days	18.2% 2/11 • Up to 24 days	0.00% 0/5 • Up to 24 days
Infections and infestations Nasopharyngitis, Upper respiratory tract infection, Rhinitis, Tooth abscess	8.7% 2/23 • Up to 24 days	12.5% 1/8 • Up to 24 days	27.3% 3/11 • Up to 24 days	0.00% 0/5 • Up to 24 days
Musculoskeletal and connective tissue disorders Back Pain, Musculoskeletal chest pain	0.00% 0/23 • Up to 24 days	12.5% 1/8 • Up to 24 days	9.1% 1/11 • Up to 24 days	20.0% 1/5 • Up to 24 days
Nervous system disorders Dizziness, Headache, Presyncope	0.00% 0/23 • Up to 24 days	25.0% 2/8 • Up to 24 days	9.1% 1/11 • Up to 24 days	20.0% 1/5 • Up to 24 days
Skin and subcutaneous tissue disorders Papule, Rash	8.7% 2/23 • Up to 24 days	0.00% 0/8 • Up to 24 days	9.1% 1/11 • Up to 24 days	0.00% 0/5 • Up to 24 days

Additional Information

Naimish Patel

AstraZeneca

Phone: +1 781 839 4061

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60