Trial Outcomes & Findings for AZD7268 Safety and Tolerability Study (NCT NCT01020799)

NCT ID: NCT01020799

Last Updated: 2012-04-17

Results Overview

MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). Change from baseline was calculated as Week 4 value minus baseline value. \[observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)\]

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 247 participants
• Primary outcome timeframe: Baseline, Week 4
• Results posted on: 2012-04-17

Participant Flow

A total of 18 centers were inititated with first patient enrolled on 16 November 2009 and last patient completed on 15 April 2010. A total of 430 patients were enrolled with 247 qualified patients allocated to randomized treatment.

Patients were required to discontinue current treatment for MDD at least 7 days prior to randomization (14 days prior to Day 1 for monoamine oxidase inhibitors [MAOIs] and 28 days prior to Day 1 for fluoxetine). Patients not taking medications for MDD at enrollment could be randomized once eligibility was confirmed.

Participant milestones

Measure	AZD7268 AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo Placebo matching both AZD7268 and escitalopram	Escitalopram Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Overall Study STARTED	98	99	50
Overall Study Patients Received Treatment	96	99	50
Overall Study Full Analysis Set	91	94	49
Overall Study COMPLETED	79	85	43
Overall Study NOT COMPLETED	19	14	7

Reasons for withdrawal

Measure	AZD7268 AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo Placebo matching both AZD7268 and escitalopram	Escitalopram Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Overall Study Adverse Event	4	3	2
Overall Study non-compliance; lack of efficacy; etc.	4	3	0
Overall Study Protocol Violation	3	2	0
Overall Study Withdrawal by Subject	2	2	3
Overall Study Lost to Follow-up	6	4	2

Baseline Characteristics

AZD7268 Safety and Tolerability Study

Baseline characteristics by cohort

Measure	AZD7268 n=98 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=99 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=50 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268	Total n=247 Participants Total of all reporting groups
Age Continuous	39.29 Years STANDARD_DEVIATION 11.63 • n=5 Participants	41.77 Years STANDARD_DEVIATION 10.02 • n=7 Participants	36.22 Years STANDARD_DEVIATION 11.29 • n=5 Participants	39.09 Years STANDARD_DEVIATION 10.98 • n=4 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	49 Participants n=7 Participants	22 Participants n=5 Participants	108 Participants n=4 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	50 Participants n=7 Participants	28 Participants n=5 Participants	139 Participants n=4 Participants
Race/Ethnicity, Customized White	66 Participants n=5 Participants	56 Participants n=7 Participants	34 Participants n=5 Participants	156 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	27 Participants n=5 Participants	35 Participants n=7 Participants	15 Participants n=5 Participants	77 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS) total score at baseline	30.9 scores on a scale STANDARD_DEVIATION 3.9 • n=5 Participants	31.4 scores on a scale STANDARD_DEVIATION 4.2 • n=7 Participants	30.8 scores on a scale STANDARD_DEVIATION 4.0 • n=5 Participants	31.03 scores on a scale STANDARD_DEVIATION 4.03 • n=4 Participants
Hamilton Rating Scale for Depression (HAM-D) total score at baseline	24.3 scores on a scale STANDARD_DEVIATION 2.9 • n=5 Participants	24.6 scores on a scale STANDARD_DEVIATION 2.8 • n=7 Participants	24.4 scores on a scale STANDARD_DEVIATION 2.8 • n=5 Participants	24.43 scores on a scale STANDARD_DEVIATION 2.83 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). Change from baseline was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From Baseline to Week 4.	-11.78 scores on a scale Standard Error 1.13 • Interval 1.13 to	-11.45 scores on a scale Standard Error 1.05 • Interval 1.05 to	-11.70 scores on a scale Standard Error 1.57 • Interval 1.57 to

SECONDARY outcome

Timeframe: Week 4

Number of patients with MADRS response at Week 4. MADRS response is defined as >=50% reduction in MADRS total score from baseline. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS response at Week 4 is calculated using last observation carried forward (LOCF). [Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Montgomery-Åsberg Depression Rating Scale (MADRS) Response	31 Participants	31 Participants	14 Participants

SECONDARY outcome

Timeframe: Week 4

Number of patients, who achieved MADRS remission at week 4. Remission is defined as a MADRS total score <= 10. MADRS total score, sum of 10 item scores (each on a 0 (best value) to 6 (worst value)scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 60 (the worst). MADRS remission at Week 4 is calculated using last observation carried forward (LOCF). [Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Montgomery-Åsberg Depression Rating Scale (MADRS) Remission	20 Participants	12 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4

HAM-D total score, sum of 17 item scores (each on a 0 to 2 or 0 to 4 scale), assesses the severity of depressive symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Hamilton Rating Scale for Depression (HAM-D) Total Score Change From Baseline to Week 4.	-9.22 scores on a scale Standard Error 0.82 • Interval 0.82 to	-9.15 scores on a scale Standard Error 0.81 • Interval 0.81 to	-9.84 scores on a scale Standard Error 0.99 • Interval 0.99 to

SECONDARY outcome

Timeframe: Baseline, Week 4

CGI-S assesses global illness severity, i.e. the patient's current clinical state, on a continuous scale from 1 ("Normal, not ill") to 7 ("Among the most extremely ill patients"). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Clinical Global Impression - Severity (CGI-S) Score Change From Baseline	-1.26 scores on a scale Standard Error 0.13 • Interval 0.13 to	-1.15 scores on a scale Standard Error 0.13 • Interval 0.13 to	-1.31 scores on a scale Standard Error 0.17 • Interval 0.17 to

SECONDARY outcome

Timeframe: Baseline, Week 4

HAM-A total score, sum of 14 item scores (each on a 0 to 4 scale), assesses the severity of anxiety symptoms on a continuous scale from 0 (the best) to 52 (the worst). Change from baseline to Week 4 was calculated as Week 4 value minus baseline value. [observed cases, Mixed Model Repeated Measurement (MMRM), Full Analysis Set (FAS)]

Outcome measures

Measure	AZD7268 n=91 Participants AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=94 Participants Placebo matching both AZD7268 and escitalopram	Escitalopram n=49 Participants Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change From Baseline	-5.30 scores on a scale Standard Error 0.60 • Interval 0.6 to	-4.66 scores on a scale Standard Error 0.61 • Interval 0.61 to	-6.15 scores on a scale Standard Error 0.78 • Interval 0.78 to

Adverse Events

AZD7268

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Escitalopram

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AZD7268 n=96 participants at risk AZD7268 15 mg twice per day (BID), placebo matching escitalopram	Placebo n=99 participants at risk Placebo matching both AZD7268 and escitalopram	Escitalopram n=50 participants at risk Escitalopram 20 mg once per day(QD) Placebo matching AZD7268
Nervous system disorders Headache	9.4% 9/96	15.2% 15/99	14.0% 7/50
General disorders Fatigue	5.2% 5/96	1.0% 1/99	2.0% 1/50
Nervous system disorders Somnolence	4.2% 4/96	5.1% 5/99	6.0% 3/50
Infections and infestations Nasopharyngitis	3.1% 3/96	5.1% 5/99	6.0% 3/50
Infections and infestations Upper Respiratory Tract Infection	3.1% 3/96	3.0% 3/99	6.0% 3/50
Gastrointestinal disorders Diarrhoea	4.2% 4/96	4.0% 4/99	14.0% 7/50
Gastrointestinal disorders Nausea	3.1% 3/96	4.0% 4/99	14.0% 7/50
Gastrointestinal disorders Dry Mouth	15.6% 15/96	9.1% 9/99	6.0% 3/50
Psychiatric disorders Libido Decreased	0.00% 0/96	1.0% 1/99	6.0% 3/50

Additional Information

Gerard Lynch

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication or presentation of results until the earlier of the publication of the first multi-center publication and the second anniversary of the completion of the multi-center study at all sites. Sponsor must receive a copy of proposed manuscript for review and comment at least 60 days prior to its submission for publication or presentation.
• Publication restrictions are in place

Restriction type: OTHER