A Study of the Safety and Tolerability of AZD5213 Effect on Sleep for Patients With Alzheimer's/Cognitive Impairment

A Phase IIa Safety and Tolerability Study to Investigate the Effect on Sleep of 3 Doses of AZD5213 and Placebo in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment During 4 Weeks of Treatment, Placebo-Controlled

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01548287

Enrollment

164

Registered

2012-03-08

Start date

2012-04-30

Completion date

2013-01-31

Last updated

2017-02-07

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

Conditions

Mild Alzheimer's Disease, Mild Cognitive Impairment

Keywords

Mild Cognitive Impairment, Mild Alzheimer's disease, Safety, Tolerability

Brief summary

This is a study where AZD5213 or placebo is given to patients with Mild Alzheimer's Disease or Mild Cognitive Impairment in a blinded and random assignment. The main study objective is to estimate the relationship of sleep duration versus dose after 4 weeks of treatment.

Detailed description

A Phase IIa Safety and Tolerability Study to Investigate the Effect on Sleep of 3 Doses of AZD5213 and Placebo in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment During 4 Weeks of Treatment, Designed as a Randomized, Double-Blind, Multi-Center, Parallel Group, Placebo-Controlled Study

Interventions

DRUGAZD5213

AZD5213 doseA daily

OTHERPlacebo

Placebo tablet daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

50 Years to 85 Years

Healthy volunteers

Inclusion criteria

* Patient and study partner to sign informed consent before initiation of any study-related procedures. * Clinical diagnosis of Alzheimers (AD) or mild cognitive impairment (MCI) disease. * Single caregiver for at least 6 months prior to Screening, capable of accompanying the patient on clinic visits as needed. The caregiver must either be living with or visiting the patient at least 10 hours per week, split over multiple (at least 2) days, for the duration of the study. * Single study partner, for at least several months prior to Screening, capable of accompanying the patient on clinic visits as needed. The study partner must either be living with or visiting the patient at least 3 days per week for the duration of the study. * A body mass index (BMI=weight/height2) of 18 kg/m2 to 32 kg/m2.

Exclusion criteria

* Significant neurological disease or dementia other than AD or MCI. * Current episode or symptoms of major depressive disorder or other major psychiatric disorder. * History of self-reported sleep duration of less than 4 hours per night or less than 4 hours average total sleep time per night during Baseline PSG assessment. * History or present symptoms of a sleeping disorder such as sleep apnea. * History of cancer in the last 5 years. * Use of anti-AD drugs (including off-label drugs and herbal medications) with the exception of donepezil, memantine, and/or rivastigmine transdermal system, as monotherapy or in combination in the following conditions: treatment with donepezil (5 mg to 10 mg daily), memantine, and/or rivastigmine transdermal system or combination regimens for at least 3 months and a stable dose(s) for the last 2 months prior to randomization is allowed.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Total Sleep Time (TST) After 4 Weeks of Treatment, Based on PSG Measurement.	Baseline and Week 4.	Total sleep time (TST) is defined as the total time in minutes, that subjects were determined to be in a sleep state by polysomnography (PSG) measurement.

Secondary

Measure	Time frame	Description
Change From Baseline in Sleep Efficiency After 4 Weeks of Treatment, Based on PSG Measurements.	Baseline and Week 4.	—
Change From Baseline in Latency to Persistent Sleep After 4 Weeks of Treatment, Based on PSG Measurements.	Baseline and Week 4.	—
Change From Baseline in Night Total Sleep Time After 4 Weeks of Treatment, Based on Actigraphy Recording.	Baseline and Week 4.	Change from baseline in night total sleep time after 4 weeks of treatment: assessed if valid baseline and week 4 actigraphy data
Change From Baseline in Latency of Persistent Sleep After 4 Weeks of Treatment, Based on Actigraphy Recording.	Baseline and Week 4.	Change from baseline in latency of persistent sleep after 4 weeks of treatment, based on participants with valid baseline and week 4 actigraphy data
Change From Baseline in Sleep Efficiency After 4 Weeks of Treatment, Based on Actigraphy Recording.	Baseline and Week 4.	Change from baseline in sleep efficiency after 4 weeks of treatment, based on participants with valid baseline and week 4 actigraphy data

Countries

United States

Participant flow

Pre-assignment details

164 subjects signed informed consent and 83 failed to qualify at the first screening visit for participation in the study.

Participants by arm

Arm	Count
AZD5213 Dose A AZD5213 AZD 0.5 mg daily	19
AZD5213 Dose B AZD 5213 2.0 mg daily	22
AZD5213 Dose C AZD5213 6.0 mg daily	20
Placebo Placebo daily	20
Total	81

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG004
Randomized Period	Adverse Event	2	5	0
Randomized Period	Did not meet inclusion criteria	0	2	0
Screening	Did not meet eligibility criteria	0	0	74
Screening	No reason provided	0	0	9

Baseline characteristics

Characteristic	AZD5213 Dose A	AZD5213 Dose B	AZD5213 Dose C	Placebo	Total
Age, Continuous	66.1 years STANDARD_DEVIATION 8.02	65.1 years STANDARD_DEVIATION 8.04	69.3 years STANDARD_DEVIATION 10.32	64.2 years STANDARD_DEVIATION 7.62	66.1 years STANDARD_DEVIATION 8.62
Alzheimers disease (AD)/Mild cognitive impairment (MCI) AD	3 Participants	6 Participants	5 Participants	5 Participants	19 Participants
Alzheimers disease (AD)/Mild cognitive impairment (MCI) MCI	16 Participants	16 Participants	15 Participants	15 Participants	62 Participants
Concomitant donepezil administration No	17 Participants	21 Participants	17 Participants	17 Participants	72 Participants
Concomitant donepezil administration Yes	2 Participants	1 Participants	3 Participants	3 Participants	9 Participants
Gender Female	12 Participants	16 Participants	13 Participants	15 Participants	56 Participants
Gender Male	7 Participants	6 Participants	7 Participants	5 Participants	25 Participants
Mini-Mental State Examination	27.2 Scores on scale STANDARD_DEVIATION 1.38	27.0 Scores on scale STANDARD_DEVIATION 2.01	26.1 Scores on scale STANDARD_DEVIATION 1.62	27.0 Scores on scale STANDARD_DEVIATION 1.88	26.8 Scores on scale STANDARD_DEVIATION 1.77

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 19	11 / 22	13 / 20	8 / 20
serious Total, serious adverse events	0 / 19	0 / 22	1 / 20	0 / 20

Outcome results

Primary

Change From Baseline in Total Sleep Time (TST) After 4 Weeks of Treatment, Based on PSG Measurement.

Total sleep time (TST) is defined as the total time in minutes, that subjects were determined to be in a sleep state by polysomnography (PSG) measurement.