Pharmacokinetic and Safety Study of Travoprost 0.004% in Pediatric Glaucoma Patients

• ClinicalTrials.gov Identifier: NCT01658839
• Recruitment Status: Completed
• First Posted: August 7, 2012
• Results First Posted: July 21, 2014
• Last Update Posted: April 1, 2016
• Sponsor: Alcon Research
• Information provided by (Responsible Party): Alcon Research

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Glaucoma; Ocular Hypertension
• Intervention: Drug: Travoprost ophthalmic solution, 0.004% (new formulation)
• Enrollment: 25

Participant Flow

Recruitment Details	Participants were recruited from 4 investigational centers located in the US, 1 located in France, 1 located in Spain, and 1 located in Saudi Arabia.
Pre-assignment Details	Twenty-five participants were enrolled and completed the study. This reporting group includes all enrolled participants (25).

Arm/Group Title	Travoprost
Arm/Group Description	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Period Title: Overall Study
Started	25
Completed	25
Not Completed	0

Baseline Characteristics

Arm/Group Title		Travoprost
Arm/Group Description		Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Baseline Participants		25
Baseline Analysis Population Description		This analysis population includes all enrolled participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants
		9.9 (5.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants
	Female	12 48.0%
	Male	13 52.0%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Travoprost Free Acid Plasma Concentration (Cmax)
Description	Travoprost free acid plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). Cmax was calculated for each participant with at least 1 quantifiable time point.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: ng/mL
Overall (n=11)	0.0256 (0.0158)
2 mo to < 3 years (n=2)	0.0471 (0.0105)
3 to <12 years (n=6)	0.0258 (0.0128)
12 to <18 years (n=3)	0.0109 (0.000046)

2. Primary Outcome

Title	Time to Reach Cmax (Tmax)
Description	Analyte plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). Tmax was calculated for each participant with at least 1 quantifiable time point.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: hours
Overall (n=11)	0.25 (0.15)
2 mo to <3 years (n=2)	0.26 (0.11)
3 to <12 years (n=6)	0.17 (0.00)
12 to <18 years (n=3)	0.39 (0.26)

3. Primary Outcome

Title	Time to Last Measurable Concentration (Tlast)
Description	Analyte plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). Tlast was calculated for each participant with at least 1 quantifiable time point.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: hours
Overall (n=11)	0.42 (0.35)
2 mo to <3 years (n=2)	0.34 (0.01)
3 to <12 years (n=6)	0.46 (0.47)
12 to <18 years (n=3)	0.39 (0.26)

4. Primary Outcome

Title	Area Under the Analyte Plasma Concentration-time Curve to the Last Quantifiable Sampling Time Point [AUC(0-tlast)]
Description	Analyte plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). AUC(0-tlast) was calculated for each participant with at least 2 quantifiable time points.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	6
Mean (Standard Deviation); Unit of Measure: ng*hr/mL
Overall (n=6)	0.0116 (0.0099)
2 mo to <3 years (n=2)	0.0101 (0.0014)
3 to <12 years (n=4)	0.0123 (0.0127)

5. Primary Outcome

Title	Area Under the Analyte Plasma Concentration-time Curve Over the Dosing Interval (Inf)[AUC(0-∞)]
Description	Analyte plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). AUC(0-∞) was calculated for each participant with at least 3 quantifiable time points.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng*hr/mL
Overall (n=1)	0.0389 [1] (NA)
3 to <12 years (n=1)	0.0389 [1] (NA)

[1]

Standard deviation was not estimated

6. Primary Outcome

Title	Half-life (t½)
Description	Analyte plasma concentrations at each collection time point (predose, 10, 20, 40, 80 minutes postdose) were quantitated using a high performance liquid chromatography/tandem mass spectrometry method (HPLC/MS/MS). T½ was calculated for each participant with at least 3 quantifiable time points.
Time Frame	Day 7, Up to 80 minutes postdose

Outcome Measure Data

Analysis Population Description

This analysis group includes all participants who received at least 2 doses of the study drug, satisfied protocol required criteria relevant to the assessments of PK parameters, had at least 1 postdose blood draw, and for whom adequate PK data were collected (without collection or analytical deviations that would affect the integrity of the data).

Arm/Group Title	Travoprost
Arm/Group Description:	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: hours
Overall (n=1)	0.53 [1] (NA)
3 to <12 years (n=1)	0.53 [1] (NA)

[1]

Standard deviation was not estimated

Adverse Events

Time Frame	Adverse events (AEs) were collected for the duration of the study (6 months). This analysis group includes all participants who received study drug.
Adverse Event Reporting Description	An AE is defined as any untoward medical occurrence in a participant who is administered a study medication, regardless of whether or not the event has a causal relationship with the medication. Reports of AEs were obtained as solicited comments from the study participants and as observations by the study Investigator.
Arm/Group Title	Travoprost
Arm/Group Description	Travoprost ophthalmic solution, 0.004% (new formulation), one drop administered topically in the inferior cul-de-sac of the eye each morning at 9 AM (± 60 minutes) for 7 days
All-Cause Mortality
	Travoprost
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Travoprost
	Affected / at Risk (%)
Total	1/25 (4.00%)
Surgical and medical procedures
Trabeculectomy † 1	1/25 (4.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (15.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Travoprost
	Affected / at Risk (%)
Total	0/25 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

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.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.

Results Point of Contact

• Name/Title: Theresa Landry, Project Head, Clinical Trial Management
• Organization: Alcon Research, Ltd.
• Phone: 1-888-451-3937
• EMail: alcon.medinfo@alcon.com

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01658839
• Other Study ID Numbers: C-12-009; 2012-001640-22 ( EudraCT Number )
• First Submitted: August 3, 2012
• First Posted: August 7, 2012
• Results First Submitted: June 24, 2014
• Results First Posted: July 21, 2014
• Last Update Posted: April 1, 2016