Study to investigate the pharmacodynamic effect of a single dose of AZD2516 in healthy male subjects

Study identifier:D3830C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A double-blind, randomized, placebo-controlled, two-centre, phase IIa pharmacodynamic cross-over study to assess the effect of AZD2516 on the total number of reflux episodes in healthy male volunteers

Medical condition

Reflux

Phase

Phase 2

Healthy volunteers

Yes

Study drug

AZD2516, 5 mg, AZD2516, 16 mg, AZD2516, 40 mg, Placebo

Sex

Male

Actual Enrollment

Study type

Interventional

Age

18 Years - 45 Years

Date

Study Start Date: 01 May 2010

Primary Completion Date: 01 Sept 2010

Study Completion Date: 01 Sept 2010

Study design

Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Basic Science

Verification:

Verified 01 Aug 2012 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

LEUVEN, Belgium

Location

Research Site

AMSTERDAM, Netherlands

Arms	Assigned Interventions
Experimental: First 5 mg, then placebo, then 16 mg, then 40 mg period 1: AZD2516 5 mg, period 2: washout, period 3: placebo, period 4: washout, period 5: AZD2516 16 mg, period 6: washout, period 7: AZD2516 40 mg.	Drug: AZD2516, 5 mg Capsule, oral Drug: AZD2516, 16 mg Capsule, oral Drug: AZD2516, 40 mg Capsule, oral Drug: Placebo Capsule, oral
Experimental: First 40 mg, then 16 mg, then placebo, then 5 mg period 1: AZD2516 40 mg, period 2: washout, period 3: AZD2516 16 mg, period 4: washout, period 5: placebo, period 6: washout, period 7: AZD2516 5 mg.	Drug: AZD2516, 5 mg Capsule, oral Drug: AZD2516, 16 mg Capsule, oral Drug: AZD2516, 40 mg Capsule, oral Drug: Placebo Capsule, oral
Experimental: First 16 mg, then 5 mg, then 40 mg, then placebo period 1: AZD2516 16 mg, period 2: washout, period 3: AZD2516 5 mg, period 4: washout, period 5: AZD2516 40 mg, period 6: washout, period 7: placebo.	Drug: AZD2516, 5 mg Capsule, oral Drug: AZD2516, 16 mg Capsule, oral Drug: AZD2516, 40 mg Capsule, oral Drug: Placebo Capsule, oral
Experimental: First placebo, then 40 mg, then 5 mg, then 16 mg period 1: placebo, period 2: washout, period 3: AZD2516 40 mg, period 4: washout, period 5: AZD2516 5 mg, period 6: washout, period 7: AZD2516 16 mg	Drug: AZD2516, 5 mg Capsule, oral Drug: AZD2516, 16 mg Capsule, oral Drug: AZD2516, 40 mg Capsule, oral Drug: Placebo Capsule, oral

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
In total 25 participants were enrolled into the study at 2 medical centres (14 and 11 participants), 20 of them were randomised to treatment (10 at each medical centre) and all these 20 participants completed the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After enrolment, participant's eligibility for assignment to treatment was based on inclusion and exclusion criteria.

Reporting Groups

	Description
First 5 mg, then placebo, then 16 mg, then 40 mg	period 1: AZD2516 5 mg, period 2: washout, period 3: placebo, period 4: washout, period 5: AZD2516 16 mg, period 6: washout, period 7: AZD2516 40 mg.
First 40 mg, then 16 mg, then placebo, then 5 mg	period 1: AZD2516 40 mg, period 2: washout, period 3: AZD2516 16 mg, period 4: washout, period 5: placebo, period 6: washout, period 7: AZD2516 5 mg.
First 16 mg, then 5 mg, then 40 mg, then placebo	period 1: AZD2516 16 mg, period 2: washout, period 3: AZD2516 5 mg, period 4: washout, period 5: AZD2516 40 mg, period 6: washout, period 7: placebo.
First placebo, then 40 mg, then 5 mg, then 16 mg	period 1: placebo, period 2: washout, period 3: AZD2516 40 mg, period 4: washout, period 5: AZD2516 5 mg, period 6: washout, period 7: AZD2516 16 mg

Participant Flow for 7 periods

Period 1: Period 1 - First Intervention

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 2: Period 2 - Washout

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 3: Period 3- Second Intervention

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 4: Period 4 - Washout

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 5: Period 5 - Third Intervention

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 6: Period 6 - Washout

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Period 7: Period 7 - Fourth Intervention

	First 5 mg, then placebo, then 16 mg, then 40 mg	First 40 mg, then 16 mg, then placebo, then 5 mg	First 16 mg, then 5 mg, then 40 mg, then placebo	First placebo, then 40 mg, then 5 mg, then 16 mg
STARTED	4	7	4	5
COMPLETED	4	7	4	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Baseline Measures

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo	Total
Number of Participants [units: Participants]	4	7	4	5	20
Age Continuous [units: years] Mean ± Standard Deviation	31 ± 9.6	25 ± 4.5	28.8 ± 5.9	23 ± 4.2	26.95 ± 6.3
Gender, Male/Female [units: Participants]
Female	0	0	0	0	0
Male	4	7	4	5	20

Outcome Measures

1. Primary Outcome Measure: Reflux episodes 0 to 3 hours post meal [ Time Frame: 0 to 3 hours post meal ]

Measure Type	Primary
Measure Name	Reflux episodes 0 to 3 hours post meal
Measure Description	Total number of reflux episodes 0 to 3 hours post meal
Time Frame	0 to 3 hours post meal
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from two subjects (one in arm AZD2516 5 mg, and one in arm Placebo) were excluded from efficacy analysis due to incorrect medication received.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	19	20	20	19
Reflux episodes 0 to 3 hours post meal [units: Episodes] Geometric Mean (Full Range)	15.1 (1 to 149)	12.5 (0 to 50)	11.0 (0 to 41)	12.7 (0 to 40)

No statistical analysis provided for Reflux episodes 0 to 3 hours post meal

2. Secondary Outcome Measure: Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 hours post meal [ Time Frame: 0 to 3 hours post meal ]

Measure Type	Secondary
Measure Name	Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 hours post meal
Measure Description	Number of TLESRs 0 to 3 hours post meal were calculated based upon the manometric analysis fpr the 3-hour post-meal period.
Time Frame	0 to 3 hours post meal
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from two subjects were excluded from efficacy analysis due to incorrect medication received Data from five visits from two subject were excluded form analysis due to deviations caused by technical problems.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	18	19	18	18
Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 hours post meal [units: relaxations] Geometric Mean (Full Range)	16.9 (8 to 51)	16.2 (9 to 26)	10.4 (2 to 31)	16.8 (9 to 33)

No statistical analysis provided for Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 hours post meal

3. Secondary Outcome Measure: Area under the plasma concentration curve(AUC) [ Time Frame: 0 to 12 hours post dose ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration curve(AUC)
Measure Description	Area under the plasma concentration vs. time curve from time zero to 12-hours post dose calculated by loglinear trapezoidal method
Time Frame	0 to 12 hours post dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	19	20	20	0
Area under the plasma concentration curve(AUC) [units: nmol*h/L] Geometric Mean (95% Confidence Interval)	251.5 (188.4 to 335.7)	906.6 (732.7 to 1122)	2825 (2185 to 3653)

No statistical analysis provided for Area under the plasma concentration curve(AUC)

4. Secondary Outcome Measure: Average Plasma Concentration (C average) [ Time Frame: 1 to 4 hours post dose ]

Measure Type	Secondary
Measure Name	Average Plasma Concentration (C average)
Measure Description	Average plasma concentration
Time Frame	1 to 4 hours post dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	19	20	20	0
Average Plasma Concentration (C average) [units: nmol/L] Geometric Mean (95% Confidence Interval)	45.46 (35.04 to 58.98)	175.8 (142.4 to 217.1)	506.8 (405.0 to 634.3)

No statistical analysis provided for Average Plasma Concentration (C average)

5. Secondary Outcome Measure: Maximum Plasma Concentration (Cmax) [ Time Frame: 0 to 12 hours post dose ]

Measure Type	Secondary
Measure Name	Maximum Plasma Concentration (Cmax)
Measure Description	Maximum plasma concentration
Time Frame	0 to 12 hours post dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	19	20	20	0
Maximum Plasma Concentration (Cmax) [units: nmol/L] Geometric Mean (95% Confidence Interval)	103.8 (76.09 to 141.5)	378.0 (315.0 to 453.5)	911.7 (767.3 to 1083)

No statistical analysis provided for Maximum Plasma Concentration (Cmax)

6. Secondary Outcome Measure: Time to maximum plasma concentration (Tmax) [ Time Frame: 0 to 12 hours post dose ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration (Tmax)
Measure Description	Time to maximum plasma concentration (Tmax)
Time Frame	0 to 12 hours post dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	19	20	20	0
Time to maximum plasma concentration (Tmax) [units: hours] Median (Full Range)	0.750 (0.500 to 4.000)	0.750 (0.500 to 1.250)	1.000 (0.500 to 4.000)

No statistical analysis provided for Time to maximum plasma concentration (Tmax)

7. Secondary Outcome Measure: Terminal half-life (T half) [ Time Frame: 0 to 12 hours post dose ]

Measure Type	Secondary
Measure Name	Terminal half-life (T half)
Measure Description	Terminal half-life (T half)
Time Frame	0 to 12 hours post dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received. Two samples were not analyzed for T half due to technical reasons.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	17	20	20	0
Terminal half-life (T half) [units: hours] Geometric Mean (95% Confidence Interval)	1.221 (1.042 to 1.430)	1.416 (1.222 to 1.640)	1.584 (1.414 to 1.774)

No statistical analysis provided for Terminal half-life (T half)

8. Secondary Outcome Measure: Clinically relevant change of laboratory variables [ Time Frame: Pre-entry to follow-up ]

Measure Type	Secondary
Measure Name	Clinically relevant change of laboratory variables
Measure Description	Number of participants with clinically relevant change of laboratory variables as judged by the responsible medical officer.
Time Frame	Pre-entry to follow-up
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Measured Values

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Number of Participants Analyzed [units:participants]	20	20	20	20
Clinically relevant change of laboratory variables [units: Participants]	0	0	0	0

No statistical analysis provided for Clinically relevant change of laboratory variables

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Serious Adverse Events

	AZD2516 5 mg	AZD2516 16 mg	AZD2516 40 mg	Placebo
Total, serious adverse events
# participants affected / at risk	0/20 (0.00%)	0/20 (0.00%)	0/20 (0.00%)	0/20 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
AZD2516 5 mg	Loading dose: 3 * AZD2516 1 mg capsules. Maintenance doses: 1 * AZD2516 1 mg capsule, 2 * placebo capsules and 1 * AZD2516 1 mg capsule, 2 * placebo capsules.
AZD2516 16 mg	Loading dose: 2 * AZD2516 5mg capsule, 1 * placebo capsule. Maintenance dose: 3 * AZD2516 1 mg capsule and 3 * AZD2516 1 mg capsule.
AZD2516 40 mg	Loading dose: 2 * AZD2616 10 mg capsules, 1 * placebo capsule. Maintenance dose: 2 * AZD2616 5 mg capsules, 1 * placebo capsule and 2 * AZD2616 5 mg capsules, 1 * placebo capsule.
Placebo	Loading dose: 3 * placebo capsules. Maintenance dose: 3 * placebo capsules and 3 * placebo capsules.

Other Adverse Events

AZD2516 5 mg

AZD2516 16 mg

AZD2516 40 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

4/20 (20.00%)

8/20 (40.00%)

12/20 (60.00%)

3/20 (15.00%)

Nervous system disorders

Disturbance In Attention¹

# participants affected / at risk

2/20 (10.00%)

5/20 (25.00%)

4/20 (20.00%)

0/20 (0.00%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

7/20 (35.00%)

0/20 (0.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

1/20 (5.00%)

3/20 (15.00%)

2/20 (10.00%)

0/20 (0.00%)

Nervous system disorders

Balance Disorder¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Nervous system disorders

Paraesthesia¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Nervous system disorders

Sinus Headache¹

# participants affected / at risk

1/20 (5.00%)

0/20 (0.00%)

Nervous system disorders

Somnolence¹

# participants affected / at risk

1/20 (5.00%)

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

2/20 (10.00%)

Gastrointestinal disorders

Abdominal Pain¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Gastrointestinal disorders

Gastrointestinal Pain¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

Psychiatric disorders

Euphoric Mood¹

# participants affected / at risk

0/20 (0.00%)

2/20 (10.00%)

0/20 (0.00%)

Psychiatric disorders

Daydreaming¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Eye disorders

Diplopia¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Eye disorders

Vision Blurred¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Ear and labyrinth disorders

Vertigo¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

0/20 (0.00%)

Renal and urinary disorders

Pyuria¹

# participants affected / at risk

0/20 (0.00%)

1/20 (5.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
Phone	+44 1625 518062
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=330&filename=CSR-D3830C00001.pdf
Download
CSR-D3830C00001.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Mark Berner Hansen

AstraZeneca R&D Molndal

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=330&filename=CSR-D3830C00001.pdf

CSR-D3830C00001.pdf

Trial Results Summaries