A Phase IIa Study to Assess the Tolerability, Safety, and Efficacy of AZD4017 for Raised Intra-ocular Pressure

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01173471

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of systemically administered AZD4017, compared with placebo, over a 28-day period in patients with raised intra-ocular pressure (IOP).

Condition or Disease	Intervention/Treatment	Phase
Raised Intraocular Pressure	Drug: AZD4017 Drug: Placebo Drug: AZD4017 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

A Double Masked, Placebo Controlled, Randomised, Parallel Group Phase IIa Study to Assess the Tolerability, Safety, and Efficacy of AZD4017 for Raised Intra-Ocular Pressure

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1) AZD4017 Europe: 200 mg AZD4017	Drug: AZD4017 tablet, oral, one tablet once daily, 28 days
Placebo Comparator: 2) Placebo Europe: placebo	Drug: Placebo matching placebo tablet, oral, one tablet once daily, 28 days
Experimental: 3) AZD4017 USA: 800 mg AZD4017	Drug: AZD4017 tablet, oral 2 tablets twice daily, 28 days
Placebo Comparator: 4) Placebo USA: placebo	Drug: Placebo matching placebo tablets, oral, 2 tablets twice daily, 28 days

Outcome Measures

Primary Outcome Measures

Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment [Baseline to 4 weeks]

Secondary Outcome Measures

Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment [Baseline to 4 weeks]
Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment [Baseline to 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have a diagnosis of intra-ocular hypertension (raised IOP), or primary open-angle glaucoma (POAG), with IOP >20 mmHg and ≤36 mmHg in the study eye, and is currently prescribed a stable dose of a single anti-glaucoma medication that began at least 30 days prior to the screening visit; OR
Must have a diagnosis of intra-ocular hypertension (raised IOP), defined as an IOP ≥22 mmHg and ≤36 mmHg in the study eye while not on anti-glaucoma medication
Male patients must be willing to use barrier contraception with spermicide, ie, condoms, from the day of first dosing until 3 months after dosing with IP
Placebo treatment for duration of the study must not be considered detrimental to the patient

Exclusion Criteria:

Have uncontrolled intra-ocular hypertension (>36 mmHg)
Have experienced a significant visual field loss or showed evidence of progressive visual field loss within the last year (as defined by >1 dB/yr average loss or vision threatening new defect)
Have had severe eye trauma at any time

Contacts and Locations

Locations

	Site	City	State	Country
1	Research Site	Newport Beach	California	United States
2	Research Site	Atlanta	Georgia	United States
3	Research Site	Morrow	Georgia	United States
4	Research Site	Overland Park	Kansas	United States
5	Research Site	Charlotte	North Carolina	United States
6	Research Site	Durham	North Carolina	United States
7	Research Site	Memphis	Tennessee	United States
8	Research Site	Lund		Sweden
9	Research Site	Molndal		Sweden
10	Research Site	Stockholm		Sweden
11	Research Site	Nottingham		United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director: Heather Bryson, PhD, AstraZeneca R&D
Study Director: Tony Ho, MD, AstraZeneca R&D

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT01173471

Other Study ID Numbers:

D4250C00001
2010-020932-20

First Posted:

Aug 2, 2010

Last Update Posted:

Feb 14, 2014

Last Verified:

Jan 1, 2014

Keywords provided by AstraZeneca

Raised intraocular pressure

Additional relevant MeSH terms:

Ocular Hypertension

Niacinamide

Study Results

Participant Flow

Recruitment Details	This multicenter study was conducted in 19 centers in the US, UK, and Sweden between 13 December 2010 and 06 November 2012. A total of 117 patients were screened in the study and of these, 50 were randomized into the double-blind treatment period.
Pre-assignment Detail	Diagnosis of intra-ocular hypertension (raised IOP), or POAG, with IOP >20 mmHg and =<36 mmHg, and currently prescribed a stable dose of one anti-glaucoma medication that began at least 30 days prior to the screening visit or a diagnosis of intra-ocular hypertension, defined as an IOP >22 mmHg and =<36 mmHg while not on anti-glaucoma medication.

Arm/Group Title	Placebo OD	AZD4017 200 mg OD	Placebo BID	AZD4017 400 mg BID
Arm/Group Description	Placebo once daily	AZD4017 200 mg once daily	Placebo twice daily	AZD4017 400 mg twice daily
Period Title: Overall Study
STARTED	6	7	18	19
Received Treatment	6	7	18	19
Completed Treatment	4	7	15	18
COMPLETED	4	7	15	18
NOT COMPLETED	2	0	3	1

Baseline Characteristics

Arm/Group Title	Placebo OD	AZD4017 200 mg OD	Placebo BID	AZD4017 400 mg BID	Total
Arm/Group Description	Placebo once daily	AZD4017 200 mg once daily	Placebo twice daily	AZD4017 400 mg twice daily	Total of all reporting groups
Overall Participants	6	7	18	19	50
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63 (6.7)	63 (8.7)	57 (15.1)	65 (10.1)	61 (11.9)
Age, Customized (Number) [Number]
<50 years	0 0%	1 14.3%	5 27.8%	2 10.5%	8 16%
>=50-<65 years	3 50%	4 57.1%	6 33.3%	5 26.3%	18 36%
>=65 years	3 50%	2 28.6%	7 38.9%	12 63.2%	24 48%
Sex: Female, Male (Count of Participants)
Female	2 33.3%	3 42.9%	9 50%	11 57.9%	25 50%
Male	4 66.7%	4 57.1%	9 50%	8 42.1%	25 50%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 5.6%	0 0%	1 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	5 27.8%	5 26.3%	10 20%
White	6 100%	7 100%	12 66.7%	14 73.7%	39 78%
Other	0 0%	0 0%	0 0%	0 0%	0 0%
Missing	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Number) [Number]
United Kingdom	2 33.3%	4 57.1%	0 0%	0 0%	6 12%
Sweden	4 66.7%	3 42.9%	0 0%	0 0%	7 14%
United States	0 0%	0 0%	18 100%	19 100%	37 74%
Stratification factor (Number) [Number]
Add-on to intra-ocular pressure medication	0 0%	1 14.3%	8 44.4%	9 47.4%	18 36%
Not on intra-ocular pressure medication	6 100%	6 85.7%	10 55.6%	10 52.6%	32 64%

Outcome Measures

1. Primary Outcome

Title	Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment
Description
Time Frame	Baseline to 4 weeks

Outcome Measure Data

Analysis Population Description
Efficacy analysis set

Arm/Group Title	Placebo OD	AZD4017 200 mg OD	Placebo BID	AZD4017 400 mg BID
Arm/Group Description	Placebo once daily	AZD4017 200 mg once daily	Placebo twice daily	AZD4017 400 mg twice daily
Measure Participants	6	7	16	19
Least Squares Mean (95% Confidence Interval) [Percentage change]	0.8	-0.4	-8.1	-11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo OD, AZD4017 200 mg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.822
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95% -15.2 to 12.6
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.352
	Estimation Comments	Difference is (AZD4017 200 mg OD - Placebo OD)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, AZD4017 400 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.413
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95% -10.1 to 4.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.516
	Estimation Comments	Difference is (AZD4017 400 mg BID - Placebo BID)

2. Secondary Outcome

Title	Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment
Description
Time Frame	Baseline to 4 weeks

Outcome Measure Data

Analysis Population Description
Efficacy analysis set

Arm/Group Title	Placebo OD	AZD4017 200 mg OD	Placebo BID	AZD4017 400 mg BID
Arm/Group Description	Placebo once daily	AZD4017 200 mg once daily	Placebo twice daily	AZD4017 400 mg twice daily
Measure Participants	6	7	18	19
>= 20% decrease in intra-ocular pressure	0 0%	0 0%	1 5.6%	4 21.1%
>= 30% decrease in intra-ocular pressure	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment
Description
Time Frame	Baseline to 4 weeks

Outcome Measure Data

Analysis Population Description
Efficacy analysis set

Arm/Group Title	Placebo OD	AZD4017 200 mg OD	Placebo BID	AZD4017 400 mg BID
Arm/Group Description	Placebo once daily	AZD4017 200 mg once daily	Placebo twice daily	AZD4017 400 mg twice daily
Measure Participants	6	7	16	19
Least Squares Mean (95% Confidence Interval) [mmHg]	0.1	-0.4	-1.9	-2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo OD, AZD4017 200 mg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.758
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95% -4.8 to 3.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.570
	Estimation Comments	Difference is (AZD4017 200 mg OD - Placebo OD)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, AZD4017 400 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.467
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -2.5 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.909
	Estimation Comments	Difference is (AZD4017 400 mg BID - Placebo BID)

Adverse Events

	Placebo OD		AZD4017 200 mg OD		Placebo BID		AZD4017 400 mg BID
Time Frame	4-week treatment period.
Adverse Event Reporting Description	All patients were required to return for a mandatory follow-up visit (Visit 8) between 14 and 21 days, inclusive, after the last dose of study medication. Any ongoing adverse events (AEs) at the follow-up visit were followed until resolution, until the AE stabilized, until it was otherwise explained, or until the patient was lost to follow-up.

Arm/Group Title	Placebo OD		AZD4017 200 mg OD		Placebo BID		AZD4017 400 mg BID
Arm/Group Description	Placebo once daily		AZD4017 200 mg once daily		Placebo twice daily		AZD4017 400 mg twice daily
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo OD		AZD4017 200 mg OD		Placebo BID		AZD4017 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)		0/18 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Placebo OD		AZD4017 200 mg OD		Placebo BID		AZD4017 400 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		3/7 (42.9%)		5/18 (27.8%)		7/19 (36.8%)
Eye disorders
BLEPHARITIS	1/6 (16.7%)	1	0/7 (0%)	0	0/18 (0%)	0	0/19 (0%)	0
CONJUNCTIVAL HAEMORRHAGE	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
CONJUNCTIVAL HYPERAEMIA	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
DELLEN	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
DRY EYE	1/6 (16.7%)	1	0/7 (0%)	0	0/18 (0%)	0	0/19 (0%)	0
EYE PAIN	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
PHOTOPHOBIA	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
VITREOUS DETACHMENT	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	1/19 (5.3%)	1
VOMITING	0/6 (0%)	0	2/7 (28.6%)	2	0/18 (0%)	0	0/19 (0%)	0
DRY MOUTH	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
DYSPEPSIA	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
LIP PRURITUS	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
General disorders
FATIGUE	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	1/19 (5.3%)	1
Infections and infestations
ASYMPTOMATIC BACTERIURIA	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
CONJUNCTIVITIS INFECTIVE	1/6 (16.7%)	1	0/7 (0%)	0	0/18 (0%)	0	0/19 (0%)	0
GASTROINTESTINAL INFECTION	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
INFECTED BITES	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
NASOPHARYNGITIS	1/6 (16.7%)	1	0/7 (0%)	0	0/18 (0%)	0	0/19 (0%)	0
URINARY TRACT INFECTION	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
Injury, poisoning and procedural complications
JOINT INJURY	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
Investigations
INTRAOCULAR PRESSURE INCREASED	2/6 (33.3%)	2	0/7 (0%)	0	0/18 (0%)	0	0/19 (0%)	0
Musculoskeletal and connective tissue disorders
SENSATION OF HEAVINESS	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
Nervous system disorders
BALANCE DISORDER	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
HEADACHE	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
PARAESTHESIA	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
PRESYNCOPE	0/6 (0%)	0	1/7 (14.3%)	1	0/18 (0%)	0	0/19 (0%)	0
Renal and urinary disorders
POLLAKIURIA	0/6 (0%)	0	0/7 (0%)	0	0/18 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
THROAT IRRITATION	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0
Vascular disorders
FLUSHING	0/6 (0%)	0	0/7 (0%)	0	1/18 (5.6%)	1	0/19 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Sponsor recognises that the Trust and Investigator have a responsibility under the Research Governance Framework for Health and Social Care to ensure that results of scientific interest arising from the Clinical Trial are appropriately published and disseminated. Such data will be submitted to the Sponsor for review and comment prior to publication. The Trust agrees, and shall ensure that the Investigator agrees, that all reasonable comments made by the Sponsor will be incorporated.

Results Point of Contact

Name/Title	Stuart McIntosh
Organization	AstraZeneca
Phone
Email	ClinicalTrialTransparency@astrazeneca.com

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT01173471

Other Study ID Numbers:

D4250C00001
2010-020932-20

First Posted:

Aug 2, 2010

Last Update Posted:

Feb 14, 2014

Last Verified:

Jan 1, 2014

A Phase IIa Study to Assess the Tolerability, Safety, and Efficacy of AZD4017 for Raised Intra-ocular Pressure

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact