Raised Intraocular Pressure
Conditions
Keywords
Raised intraocular pressure
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).
Interventions
DRUGAZD4017
tablet, oral, one tablet once daily, 28 days
DRUGPlacebo
matching placebo tablet, oral, one tablet once daily, 28 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | Baseline to 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Sweden, United Kingdom, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo OD Placebo once daily | 6 |
| AZD4017 200 mg OD AZD4017 200 mg once daily | 7 |
| Placebo BID Placebo twice daily | 18 |
| AZD4017 400 mg BID AZD4017 400 mg twice daily | 19 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Condition under investigation worsened | 2 | 0 | 0 | 0 |
| Overall Study | Eligibility criteria not fulfilled | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Reason given as Other | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo OD | AZD4017 200 mg OD | Placebo BID | AZD4017 400 mg BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63 Years STANDARD_DEVIATION 6.7 | 63 Years STANDARD_DEVIATION 8.7 | 57 Years STANDARD_DEVIATION 15.1 | 65 Years STANDARD_DEVIATION 10.1 | 61 Years STANDARD_DEVIATION 11.9 |
| Age, Customized >=50-<65 years | 3 Participants | 4 Participants | 6 Participants | 5 Participants | 18 Participants |
| Age, Customized <50 years | 0 Participants | 1 Participants | 5 Participants | 2 Participants | 8 Participants |
| Age, Customized >=65 years | 3 Participants | 2 Participants | 7 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 7 Participants | 12 Participants | 14 Participants | 39 Participants |
| Region of Enrollment Sweden | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 7 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 6 Participants |
| Region of Enrollment United States | 0 Participants | 0 Participants | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 9 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 9 Participants | 8 Participants | 25 Participants |
| Stratification factor Add-on to intra-ocular pressure medication | 0 Participants | 1 Participants | 8 Participants | 9 Participants | 18 Participants |
| Stratification factor Not on intra-ocular pressure medication | 6 Participants | 6 Participants | 10 Participants | 10 Participants | 32 Participants |
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 | 5 / 6 | 3 / 7 | 5 / 18 | 7 / 19 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 18 | 0 / 19 |
Outcome results
Primary
Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment
Time frame: Baseline to 4 weeks
Population: Efficacy analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo OD | Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | 0.8 Percentage change |
| AZD4017 200 mg OD | Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -0.4 Percentage change |
| Placebo BID | Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -8.1 Percentage change |
| AZD4017 400 mg BID | Percentage Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -11.0 Percentage change |
p-value: 0.82295% CI: [-15.2, 12.6]Mixed Models Analysis
p-value: 0.41395% CI: [-10.1, 4.3]Mixed Models Analysis
Secondary
Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment
Time frame: Baseline to 4 weeks
Population: Efficacy analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo OD | Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | 0.1 mmHg |
| AZD4017 200 mg OD | Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -0.4 mmHg |
| Placebo BID | Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -1.9 mmHg |
| AZD4017 400 mg BID | Change in Mean Intra-ocular Pressure Compared With Baseline After 4 Weeks Treatment | -2.6 mmHg |
p-value: 0.75895% CI: [-4.8, 3.7]Mixed Models Analysis
p-value: 0.46795% CI: [-2.5, 1.2]Mixed Models Analysis
Secondary
Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment
Time frame: Baseline to 4 weeks
Population: Efficacy analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo OD | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 20% decrease in intra-ocular pressure | 0 Participants |
| Placebo OD | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 30% decrease in intra-ocular pressure | 0 Participants |
| AZD4017 200 mg OD | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 30% decrease in intra-ocular pressure | 0 Participants |
| AZD4017 200 mg OD | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 20% decrease in intra-ocular pressure | 0 Participants |
| Placebo BID | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 20% decrease in intra-ocular pressure | 1 Participants |
| Placebo BID | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 30% decrease in intra-ocular pressure | 0 Participants |
| AZD4017 400 mg BID | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 20% decrease in intra-ocular pressure | 4 Participants |
| AZD4017 400 mg BID | Clinically Relevant Change in Intra-ocular Pressure After 4 Weeks of Treatment | >= 30% decrease in intra-ocular pressure | 0 Participants |