Infantile Hemangioma
Conditions
Keywords
Hemangioma, Infantile Hemangioma, Pharmacokinetics
Brief summary
The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.
Detailed description
Primary: Describe the efficacy of 0.25% and 0.5% topical timolol maleate Gel-forming solution (GFS) as assessed through Infantile Hemangioma (IH) changes in volume. Secondary: Describe the safety of topical timolol maleate GFS for treatment of IH.
Interventions
DRUG0.25% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution
DRUG0.5% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution
Sponsors
The Emmes Company, LLC
National Institutes of Health (NIH)
Kanecia Obie Zimmerman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 84 Days
Healthy volunteers
No
Inclusion criteria
1. Documented informed consent from legal guardian 2. 0-84 days postnatal age at time of first study dose or when enrolled into the non-intervention cohort. 3. Clinical diagnosis of superficial cutaneous or mucosal infantile hemangioma (must include all of the following): 1. Superficial lesion in the dermis 2. Thin \<2 mm in thickness 3. Small \>=5 cm at its longest dimension and \<=10cm2 4. Involves skin or keratinized mucosa
Exclusion criteria
1. History of previous treatment with any pharmacologic or laser therapy for IH 2. Ongoing therapy with an oral beta blocker or oral corticosteroid (e.g., cardiac arrhythmia, adrenal insufficiency, upper airway obstruction, tetralogy of fallot (TOF), hypertension, reactive airways disease) 3. IH that requires systemic therapy (defined by dynamic complication scale \>3) 4. IH of the non-keratinized mucosa 5. Infants with more than one hemangioma that requires therapy 6. Hemodynamically significant cardiovascular disease, as determined by the investigator 7. Known allergy to beta blockers or vehicle 8. Heart rate \<100 beats per minute at screening visit 9. Known prenatal or postnatal diagnosis of 2nd/3rd degree atrioventricular block 10. History of Reactive Airways Disease (RAD) 11. Any condition which would make the participant, in the opinion of the investigator unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 180 days | The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as \>20% and up to 80% reduction in volumetric size of hemangioma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm | 180 days | Comparison of partial response of hemangioma color (partial response or greater as assessed by VAS-color) between the two treatment arms. Partial response: \>30% and up to 80% reduction in color of hemangioma. |
| Number of Participants Who Reach Partial Response, Assessed by Volume | 30 days, 60 days, 120 days, 180 days | Assess time to partial response or greater by VAS-volume, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>20% and up to 80% reduction in volumetric size of hemangioma |
| Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 180 days | Assess time to partial response or greater by VAS-color, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>30% and up to 80% reduction in color of hemangioma |
| Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants | baseline, day 180 | Absolute change in IH-QoL score scale from Day 0 to end of study within each treatment arm. The IH-QoL score scale consists of 4 domains (physical symptom of patient, social functioning of patient, social and psychological functioning of caregiver, and emotional functioning of caregiver) and 29 items, with each item scored on a Likert scale : 0 = never a problem, 1 = almost never a problem, 2 = sometimes a problem, 3 = often a problem and 4 = almost always a problem). The total range is 0-116; the higher the total number indicates a worse outcome. |
| Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | up to 270 days | Serious adverse events and adverse events of special interest from randomization to Day 180 in infants treated with topical timolol maleate (0.25% and 0.5%) GFS for the treatment of infantile hemangioma. |
| Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 180 days | The VAS-color is a 100 mm scale used to independently grade hemangioma color. -100 indicates hemangioma is twice as intense, 0 indicates no change, and +100 indicates complete resolution. Partial response is defined as \>30% and up to 80% reduction in color of hemangioma. |
| Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm | 180 days | The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as \>20% and up to 80% reduction in volumetric size of hemangioma. |
| Change in Hemangioma Dynamic Complication Scale (HDCS) | baseline, day 180 | Absolute change in hemangioma dynamic complication scale from Day 0 to end of study within each treatment arm. The HDCS provides a 6-point severity grading system for 12 individual hemangioma-related complications (grade 0 represents absent to minimal; grade 5 = most severe). The total score ranges from 0-60. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) Analysis Measuring Volume of Distribution of Timolol in Plasma Specimen | Up to 12 hours | The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours. |
| Pharmacokinetics (PK) Analysis Measuring Clearance of Timolol in Plasma Specimen | Up to 12 hours | The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours. |
| Pharmacokinetics (PK) Analysis Measuring Maximum Concentration of Timolol in Plasma Specimen | Up to 12 hours | The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours. |
| Pharmacokinetics (PK) Analysis Measuring Area Under the Curve of Timolol in Plasma Specimen | Up to 12 hours | The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours. |
Countries
United States
Participant flow
Recruitment details
Infants who were eligible for the study based on inclusion and exclusion criteria but whose parents declined treatment of the hemangioma constituted the non-intervention arm of the study and served as a control group
Participants by arm
| Arm | Count |
|---|---|
| 0.25% Timolol Treatment Subjects assigned to this arm will be randomized to 0.25% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.25% timolol they will be changed to 0.5% timolol.
0.25% Timolol Maleate Gel Forming Solution: 50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution | 44 |
| 0.5% Timolol Treatment Subjects assigned to this arm will be randomized to 0.5% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.5% timolol the treating physician will decide to either continue 0.5% timolol or withdraw the subject and begin an alternative treatment.
0.5% Timolol Maleate Gel Forming Solution: 50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution | 51 |
| Non-Intervention Group Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group. | 10 |
| Historical Control Group To obtain sufficient age-matched controls, data and clinical photographs collected as part of a similar study (EudraCT 2013-005199-17) were included in the analysis of certain outcome measures as noted in the Analysis Population Description of those measures. | 36 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Hemangioma resolved | 1 | 0 | 0 | 0 |
| Overall Study | Ineligible | 0 | 1 | 0 | 0 |
| Overall Study | Insurance issues | 0 | 1 | 0 | 0 |
| Overall Study | Local IRB decision | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 6 | 5 | 2 | 0 |
| Overall Study | Needed to treat second hemangioma | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 4 | 1 | 0 |
| Overall Study | Study completion criteria not met | 0 | 1 | 0 | 0 |
| Overall Study | Study drug non-compliance | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | 0.25% Timolol Treatment | Total | Historical Control Group | Non-Intervention Group | 0.5% Timolol Treatment |
|---|---|---|---|---|---|
| Age, Continuous | 55.2 months STANDARD_DEVIATION 17.2 | 52.8 months STANDARD_DEVIATION 16.5 | 47.3 months STANDARD_DEVIATION 11.4 | 58.1 months STANDARD_DEVIATION 14.4 | 53.6 months STANDARD_DEVIATION 18.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 17 Participants | 0 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 87 Participants | 0 Participants | 10 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 37 Participants | 36 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 9 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 36 Participants | 36 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 95 Participants | 0 Participants | 8 Participants | 47 Participants |
| Region of Enrollment United States | 44 Participants | 141 Participants | 36 Participants | 10 Participants | 51 Participants |
| Sex: Female, Male Female | 32 Participants | 96 Participants | 26 Participants | 5 Participants | 33 Participants |
| Sex: Female, Male Male | 12 Participants | 45 Participants | 10 Participants | 5 Participants | 18 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 | 0 / 44 | 0 / 51 | 0 / 10 | 0 / 0 |
| other Total, other adverse events | 31 / 44 | 28 / 51 | 4 / 10 | 0 / 0 |
| serious Total, serious adverse events | 3 / 44 | 2 / 51 | 0 / 10 | 0 / 0 |
Outcome results
Primary
Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls
The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as \>20% and up to 80% reduction in volumetric size of hemangioma.
Time frame: 180 days
Population: The Historical Control group was included with the Non-intervention group. Excludes 8 participants (four in the 0.5% dosage and four in the historical placebo controls) with out come determined to be unevaluable as they have no reported VAS scores
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.25% Timolol Treatment | Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 24 Participants |
| 0.5% Timolol Treatment | Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 28 Participants |
| Non-Intervention Group | Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 15 Participants |
p-value: 0.020595% CI: [1.12, 6.26]Fisher Exact
p-value: 0.061995% CI: [0.91, 5.14]Fisher Exact
p-value: 0.628195% CI: [0.53, 2.82]Fisher Exact
Secondary
Change in Hemangioma Dynamic Complication Scale (HDCS)
Absolute change in hemangioma dynamic complication scale from Day 0 to end of study within each treatment arm. The HDCS provides a 6-point severity grading system for 12 individual hemangioma-related complications (grade 0 represents absent to minimal; grade 5 = most severe). The total score ranges from 0-60.
Time frame: baseline, day 180
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 0.25% Timolol Treatment | Change in Hemangioma Dynamic Complication Scale (HDCS) | 0 score on a scale |
| 0.5% Timolol Treatment | Change in Hemangioma Dynamic Complication Scale (HDCS) | -0.1 score on a scale |
| Non-Intervention Group | Change in Hemangioma Dynamic Complication Scale (HDCS) | 0 score on a scale |
Secondary
Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants
Absolute change in IH-QoL score scale from Day 0 to end of study within each treatment arm. The IH-QoL score scale consists of 4 domains (physical symptom of patient, social functioning of patient, social and psychological functioning of caregiver, and emotional functioning of caregiver) and 29 items, with each item scored on a Likert scale : 0 = never a problem, 1 = almost never a problem, 2 = sometimes a problem, 3 = often a problem and 4 = almost always a problem). The total range is 0-116; the higher the total number indicates a worse outcome.
Time frame: baseline, day 180
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.25% Timolol Treatment | Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants | 35.3 score on a scale | Standard Deviation 8.8 |
| 0.5% Timolol Treatment | Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants | 37.4 score on a scale | Standard Deviation 8.5 |
| Non-Intervention Group | Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants | 32.6 score on a scale | Standard Deviation 3.3 |
Secondary
Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm
Comparison of partial response of hemangioma color (partial response or greater as assessed by VAS-color) between the two treatment arms. Partial response: \>30% and up to 80% reduction in color of hemangioma.
Time frame: 180 days
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.25% Timolol Treatment | Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm | 32 Participants |
| 0.5% Timolol Treatment | Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm | 34 Participants |
Secondary
Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color
Assess time to partial response or greater by VAS-color, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>30% and up to 80% reduction in color of hemangioma
Time frame: 180 days
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 30-Day Visit | 17 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 60-Day Visit | 19 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 120-Day Visit | 25 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 180-Day Visit | 29 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 180-Day Visit | 30 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 30-Day Visit | 20 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 120-Day Visit | 28 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 60-Day Visit | 21 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 180-Day Visit | 5 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 60-Day Visit | 2 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 120-Day Visit | 4 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | 30-Day Visit | 0 Participants |
Secondary
Number of Participants Who Reach Partial Response, Assessed by Volume
Assess time to partial response or greater by VAS-volume, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>20% and up to 80% reduction in volumetric size of hemangioma
Time frame: 30 days, 60 days, 120 days, 180 days
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 120-Day Visit | 18 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 30-Day Visit | 12 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 180-Day Visit | 23 Participants |
| 0.25% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 60-Day Visit | 17 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 120-Day Visit | 21 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 60-Day Visit | 19 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 30-Day Visit | 14 Participants |
| 0.5% Timolol Treatment | Number of Participants Who Reach Partial Response, Assessed by Volume | 180-Day Visit | 24 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Volume | 180-Day Visit | 4 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Volume | 30-Day Visit | 0 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Volume | 60-Day Visit | 1 Participants |
| Non-Intervention Group | Number of Participants Who Reach Partial Response, Assessed by Volume | 120-Day Visit | 3 Participants |
Secondary
Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls
The VAS-color is a 100 mm scale used to independently grade hemangioma color. -100 indicates hemangioma is twice as intense, 0 indicates no change, and +100 indicates complete resolution. Partial response is defined as \>30% and up to 80% reduction in color of hemangioma.
Time frame: 180 days
Population: The Historical Control group was included with the Non-intervention group. Only participants with evaluable data were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.25% Timolol Treatment | Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 32 Participants |
| 0.5% Timolol Treatment | Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 34 Participants |
| Non-Intervention Group | Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | 19 Participants |
Secondary
Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm
The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as \>20% and up to 80% reduction in volumetric size of hemangioma.
Time frame: 180 days
Population: Only participants with evaluable data were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.25% Timolol Treatment | Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm | 24 Participants |
| 0.5% Timolol Treatment | Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm | 28 Participants |
Secondary
Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate
Serious adverse events and adverse events of special interest from randomization to Day 180 in infants treated with topical timolol maleate (0.25% and 0.5%) GFS for the treatment of infantile hemangioma.
Time frame: up to 270 days
Population: Only participants who received treatment and had evaluable data were included in this analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.25% Timolol Treatment | Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | AEs of Special Interest | 14 adverse events |
| 0.25% Timolol Treatment | Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | Serious AEs | 3 adverse events |
| 0.5% Timolol Treatment | Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | AEs of Special Interest | 14 adverse events |
| 0.5% Timolol Treatment | Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | Serious AEs | 2 adverse events |
Other Pre-specified
Pharmacokinetics (PK) Analysis Measuring Area Under the Curve of Timolol in Plasma Specimen
The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.
Time frame: Up to 12 hours
Other Pre-specified
Pharmacokinetics (PK) Analysis Measuring Clearance of Timolol in Plasma Specimen
The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.
Time frame: Up to 12 hours
Other Pre-specified
Pharmacokinetics (PK) Analysis Measuring Maximum Concentration of Timolol in Plasma Specimen
The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.
Time frame: Up to 12 hours
Other Pre-specified
Pharmacokinetics (PK) Analysis Measuring Volume of Distribution of Timolol in Plasma Specimen
The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.
Time frame: Up to 12 hours