Trial Outcomes & Findings for A Two Week Study to Assess the Tolerability of AZD9668 in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00703391)

NCT ID: NCT00703391

Last Updated: 2012-01-26

Results Overview

ALT level greater than 3 times the upper limit of normal

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)
• Results posted on: 2012-01-26

Participant Flow

First patient enrolled: 11 June 2008. Last patient completed: 09 October 2008. Single-centre study performed at a Clinical Pharmacology Unit

Participant milestones

Measure	AZD9668 AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Overall Study STARTED	12	6
Overall Study COMPLETED	12	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Two Week Study to Assess the Tolerability of AZD9668 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Baseline characteristics by cohort

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days	Total n=18 Participants Total of all reporting groups
Age Continuous	57.6 Years n=5 Participants	52.8 Years n=7 Participants	56 Years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

ALT level greater than 3 times the upper limit of normal

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Alanine Aminotransferase (ALT)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

AST level greater than 3 times the upper limit of normal

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Aspartate Aminotransferase (AST)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Creatine Kinase (CK)	2.57 IU/L Standard Deviation 19.260	-69.57 IU/L Standard Deviation 141.383

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Total Bilirubin	0.11 micromol/L Standard Deviation 2.124	-0.28 micromol/L Standard Deviation 2.563

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Creatinine level greater than the upper limit of normal

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Creatinine	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Haemoglobin (Hb)	-2.0 g/L Standard Deviation 4.73	-0.2 g/L Standard Deviation 6.18

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Reticulocytes	-0.15 relative particle count (%) Standard Deviation 2.851	1.73 relative particle count (%) Standard Deviation 1.605

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Leucocytes	-0.001 10**9/L Standard Deviation 0.8816	0.265 10**9/L Standard Deviation 0.4657

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

QTcF interval greater than 450 ms

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
QTcF (QT Interval Corrected for Heart Rate by Fridericia's Method)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

QTcF change from baseline greater than 60 ms

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
QTcF	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Change from baseline to Day 14

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
FEV1 (Forced Expiratory Volume in the First Second)	0.039 L Standard Deviation 0.2173	-0.110 L Standard Deviation 0.3043

PRIMARY outcome

Timeframe: Pre-dose on day -1 to day 15 (end of dosing)

AUC(0-12) following 14 days' dosing

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC(0-12))	7560 nM.h Interval 5820.0 to 9570.0	—

PRIMARY outcome

Timeframe: Pre-dose on day -1 to day 15 (end of dosing)

Cmax following 14 days' dosing

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Observed Peak or Maximum Plasma Concentration Following Drug Administration (Cmax)	1420 nM Interval 1030.0 to 1930.0	—

PRIMARY outcome

Timeframe: Pre-dose on day -1 to day 15 (end of dosing)

tmax following 14 days' dosing

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Time to Reach Observed Peak or Maximum Concentration Following Oral Drug Administration (Tmax)	1.01 hours Interval 0.49 to 2.01	—

PRIMARY outcome

Timeframe: Pre-dose on day -1 to day 15 (end of dosing)

t1/2 following 14 days' dosing

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Terminal Half-life of Drug in Plasma (t1/2)	5.89 hours Interval 5.0 to 6.46	—

PRIMARY outcome

Timeframe: Pre-dose on day -1 to day 15 (end of dosing)

CLR following 14 days' dosing

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
Renal Clearance of Drug From Plasma (CLR)	6.13 L/h Interval 3.49 to 8.22	—

SECONDARY outcome

Timeframe: Pre-dose day -1 to post-dose on day 14

Change from baseline to Day 14 in absolute neutrophil count

Outcome measures

Measure	AZD9668 n=7 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=4 Participants Matched placebo tablets twice daily (bid) for 14 days
Sputum Absolute Neutrophil Count	-0.4890 10**9/L Interval -1.439 to 0.439	-2.5645 10**9/L Interval -9.198 to -0.283

SECONDARY outcome

Timeframe: Pre-dose day -1 to post-dose on day 14

Change from baseline to Day 14 in percentage neutrophil count

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Sputum Differential Neutrophil Count	1.8 Percentage Interval -11.0 to 10.0	-4.25 Percentage Interval -9.0 to 8.7

SECONDARY outcome

Timeframe: Pre-dose day -1 to post-dose on day 14

Outcome measures

Measure	AZD9668 n=11 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo Matched placebo tablets twice daily (bid) for 14 days
AZD9668 Sputum Concentrations	41.7 nM Interval 26.5 to 64.3	—

SECONDARY outcome

Timeframe: Pre-dose day -1 to post-dose on day 15

Number of patients with an increase in bacteriological count from Day -1 to Day 15

Outcome measures

Measure	AZD9668 n=12 Participants AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 Participants Matched placebo tablets twice daily (bid) for 14 days
Quantitative Sputum Bacteriology	3 Participants	2 Participants

Adverse Events

AZD9668

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AZD9668 n=12 participants at risk AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Placebo n=6 participants at risk Matched placebo tablets twice daily (bid) for 14 days
Cardiac disorders Palpitations	8.3% 1/12	0.00% 0/6
Gastrointestinal disorders Diarrhoea	8.3% 1/12	0.00% 0/6
Gastrointestinal disorders Dyspepsia	0.00% 0/12	16.7% 1/6
Gastrointestinal disorders Nausea	8.3% 1/12	0.00% 0/6
Gastrointestinal disorders Vomiting	8.3% 1/12	0.00% 0/6
General disorders Chest discomfort	8.3% 1/12	0.00% 0/6
General disorders Fatigue	0.00% 0/12	16.7% 1/6
Infections and infestations Respiratory tract infection	8.3% 1/12	0.00% 0/6
Ear and labyrinth disorders Back pain	16.7% 2/12	0.00% 0/6
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 1/12	0.00% 0/6
Nervous system disorders Headache	8.3% 1/12	66.7% 4/6
Skin and subcutaneous tissue disorders Hyperhidrosis	8.3% 1/12	0.00% 0/6

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place