Safety and Efficacy Study of Bimatoprost to Treat Hypotrichosis of the Eyelashes After Application to the Eyelid Margin

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00907426
• Collaborator: (none)
• Enrollment: 368
• Locations: 2
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 184
• Patients Per Site Per Month: 8.8

Study Details

Study Description

Brief Summary

This one-year study evaluates the long-term safety and effectiveness of bimatoprost solution application to the eyelid margin (where the eyelashes meet the skin) to treat hypotrichosis of the eyelashes (inadequate or not enough eyelashes). There will be two different types of subjects participating in the study 1)those with inadequate eyelashes due to natural causes or 2) those with inadequate eyelashes following a complete course of chemotherapy treatment. There will be two treatment periods of six months each. Subjects will receive either the study medication or vehicle in either of the two treatment periods.

Condition or Disease	Intervention/Treatment	Phase
Hypotrichosis	Drug: Bimatoprost 0.03% solution; Drug: Vehicle solution	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bimatoprost 0.03% Followed by Bimatoprost 0.03% Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Drug: Bimatoprost 0.03% solution; Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).; Other Names: LATISSE™
Other: Bimatoprost 0.03% Followed by Vehicle Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Drug: Bimatoprost 0.03% solution; Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).; Other Names: LATISSE™ ; Drug: Vehicle solution; Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).; Other Names: LATISSE™
Other: Vehicle Followed by Bimatoprost 0.03% Treatment period one (0-6 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Drug: Bimatoprost 0.03% solution; Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).; Other Names: LATISSE™ ; Drug: Vehicle solution; Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).; Other Names: LATISSE™

Outcome Measures

Primary Outcome Measures

1. Percentage of Treatment Responders at Month 4 [Month 4]

   Percentage of Treatment Responders at Month 4 defined by: a) at least a 1-grade improvement from baseline in the Global Eyelash Assessment (GEA) score, AND b) at least a 3-point improvement from baseline in the total score for Domain 2 of the Eyelash Symptom Questionnaire (ESQ). The GEA 4-point scale assessed eyelash prominence from 1 (minimal) to 4 (very marked). Domain 2 of the ESQ assessed subjective attributes of confidence, attractiveness, and professionalism rated on a 5-point scale from 1 (very much disagree) to 5 (very much agree) for a total score between 3 and 15.

Secondary Outcome Measures

1. Change From Baseline in Upper Eyelash Length at Month 4 [Baseline, Month 4]

   Change from Baseline to in upper eyelash length at Month 4, measured in millimeters (mm). Data from both eyes were averaged for each subject for analysis. Changes from baseline represented by positive values indicated longer length, and changes from baseline represented by negative values indicated shorter length.

2. Change From Baseline in Average Progressive Upper Eyelash Thickness at Month 4 [Baseline, Month 4]

   Change from baseline in average progressive upper eyelash thickness at Month 4 was measured within 3 preset areas. Eyelash thickness was assessed across both eyes as an average of the 3 preset areas measured in millimeters squared (mm^2). Changes from baseline at Month 4 represented by positive values indicated increased eyelash thickness, and changes from baseline represented by negative values indicated thinner eyelash thickness.

3. Change From Baseline in Upper Eyelash Darkness at Month 4 [Baseline, Month 4]

   Change from baseline in upper eyelash darkness at Month 4 was determined by lash intensity within the spline (a narrow area approximately 5 pixels wide that bisects the area of interest). Upper eyelash darkness was measured in both eyes and averaged for analysis. Colors ranged from black=0 to white=255. Lower numbers on this continuum indicated darker colors. A negative number value change from baseline indicated increased eyelash darkening.

Other Outcome Measures

1. Percentage of Subjects With at Least a 1-Grade Improvement in Global Eyelash Assessment (GEA) Score at Month 4 [Month 4]

   Percentage of subjects with at least a 1-grade improvement in GEA score at Month 4. The GEA scale is an investigator-graded 4-point scale of overall eyelash prominence where 1=minimal, 2=moderate, 3=marked, and 4=very marked prominence.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who have inadequate eyelashes due to natural causes and are not satisfied with their eyelash appearance.

• For the post-chemotherapy population: subjects who have inadequate eyelashes following a complete course of chemotherapy treatment and are not satisfied with their eyelash appearance, are considered free of cancer and are well enough to complete the study.

Exclusion Criteria:

• Subjects with unequal right and left eyelashes, any eye disease or abnormality, eye surgery, permanent eyeliner, eyelash implants, eyelash extension application.

• Any use of over the counter or prescription use eyelash growth products.

• Subjects requiring eye drop medications for glaucoma.

• Females who are pregnant, nursing or planning a pregnancy during the study or who are of childbearing potential and not using a reliable method of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		San Diego	California	United States
2		London	England	United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00907426
• Other Study ID Numbers: 192024-038
• First Posted: May 22, 2009
• Last Update Posted: Sep 19, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Allergan: eyelashes
• Additional relevant MeSH terms: Hypotrichosis; Bimatoprost; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Bimatoprost 0.03% Followed by Bimatoprost 0.03%	Bimatoprost 0.03% Followed by Vehicle	Vehicle Followed by Bimatoprost 0.03%
Arm/Group Description	Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Treatment period one (0-6 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.
Period Title: Treatment Period 1 (0 to 6 Months)
STARTED	215	60	93
COMPLETED	195	55	84
NOT COMPLETED	20	5	9
Period Title: Treatment Period 1 (0 to 6 Months)
STARTED	195	55	84
COMPLETED	184	52	77
NOT COMPLETED	11	3	7

Baseline Characteristics

Arm/Group Title	Bimatoprost 0.03% Followed by Bimatoprost 0.03%	Bimatoprost 0.03% Followed by Vehicle	Vehicle Followed by Bimatoprost 0.03%	Total
Arm/Group Description	Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Treatment period one (0-6 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.	Total of all reporting groups
Overall Participants	215	60	93	368
Age, Customized (Number) [Number]
<45 Years	56 26%	18 30%	31 33.3%	105 28.5%
Between 45 and 65 years	151 70.2%	35 58.3%	53 57%	239 64.9%
>65 Years	8 3.7%	7 11.7%	9 9.7%	24 6.5%
Sex: Female, Male (Count of Participants)
Female	214 99.5%	58 96.7%	92 98.9%	364 98.9%
Male	1 0.5%	2 3.3%	1 1.1%	4 1.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Treatment Responders at Month 4
Description	Percentage of Treatment Responders at Month 4 defined by: a) at least a 1-grade improvement from baseline in the Global Eyelash Assessment (GEA) score, AND b) at least a 3-point improvement from baseline in the total score for Domain 2 of the Eyelash Symptom Questionnaire (ESQ). The GEA 4-point scale assessed eyelash prominence from 1 (minimal) to 4 (very marked). Domain 2 of the ESQ assessed subjective attributes of confidence, attractiveness, and professionalism rated on a 5-point scale from 1 (very much disagree) to 5 (very much agree) for a total score between 3 and 15.
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized subjects

Arm/Group Title	Bimatoprost 0.03%	Vehicle
Arm/Group Description	Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).	Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).
Measure Participants	275	93
Number [Percentage of Subjects]	39.3	10.9

2. Secondary Outcome

Title	Change From Baseline in Upper Eyelash Length at Month 4
Description	Change from Baseline to in upper eyelash length at Month 4, measured in millimeters (mm). Data from both eyes were averaged for each subject for analysis. Changes from baseline represented by positive values indicated longer length, and changes from baseline represented by negative values indicated shorter length.
Time Frame	Baseline, Month 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized subjects who had baseline and Month 4 data collected for this outcome measure

Arm/Group Title	Bimatoprost 0.03%	Vehicle
Arm/Group Description	Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).	Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).
Measure Participants	271	89
Baseline	5.40 (1.085)	5.42 (1.138)
Change from Baseline at Month 4	1.33 (1.110)	0.07 (1.015)

3. Secondary Outcome

Title	Change From Baseline in Average Progressive Upper Eyelash Thickness at Month 4
Description	Change from baseline in average progressive upper eyelash thickness at Month 4 was measured within 3 preset areas. Eyelash thickness was assessed across both eyes as an average of the 3 preset areas measured in millimeters squared (mm^2). Changes from baseline at Month 4 represented by positive values indicated increased eyelash thickness, and changes from baseline represented by negative values indicated thinner eyelash thickness.
Time Frame	Baseline, Month 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized subjects who had baseline and Month 4 data collected for this outcome measure

Arm/Group Title	Bimatoprost 0.03%	Vehicle
Arm/Group Description	Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).	Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).
Measure Participants	216	71
Baseline	0.67 (0.376)	0.82 (0.598)
Change from Baseline at Month 4	0.59 (0.471)	-0.07 (0.520)

4. Secondary Outcome

Title	Change From Baseline in Upper Eyelash Darkness at Month 4
Description	Change from baseline in upper eyelash darkness at Month 4 was determined by lash intensity within the spline (a narrow area approximately 5 pixels wide that bisects the area of interest). Upper eyelash darkness was measured in both eyes and averaged for analysis. Colors ranged from black=0 to white=255. Lower numbers on this continuum indicated darker colors. A negative number value change from baseline indicated increased eyelash darkening.
Time Frame	Baseline, Month 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized subjects who had baseline and Month 4 data collected for this outcome measure

Arm/Group Title	Bimatoprost 0.03%	Vehicle
Arm/Group Description	Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).	Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).
Measure Participants	215	70
Baseline	151.36 (24.670)	148.82 (26.445)
Change from Baseline at Month 4	-23.55 (20.787)	-2.60 (18.592)

5. Other Pre-specified Outcome

Title	Percentage of Subjects With at Least a 1-Grade Improvement in Global Eyelash Assessment (GEA) Score at Month 4
Description	Percentage of subjects with at least a 1-grade improvement in GEA score at Month 4. The GEA scale is an investigator-graded 4-point scale of overall eyelash prominence where 1=minimal, 2=moderate, 3=marked, and 4=very marked prominence.
Time Frame	Month 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized subjects who had baseline and Month 4 data collected for this outcome measure

Arm/Group Title	Bimatoprost 0.03%	Vehicle
Arm/Group Description	Once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).	Once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin).
Measure Participants	275	92
Number [Percentage of Participants]	73.8 34.3%	28.3 47.2%

Adverse Events

Adverse Event Reporting Description	The Safety Population included all subjects who received at least one dose of study medication and was used to analyze serious adverse events (SAEs) and adverse events (AEs). SAEs/AEs are reported by arm randomized, not by treatment received.
Arm/Group Title	Bimatoprost 0.03% Followed by Bimatoprost 0.03%		Bimatoprost 0.03% Followed by Vehicle		Vehicle Followed by Bimatoprost 0.03%
Arm/Group Description	Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.		Treatment period one (0-6 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin.		Treatment period one (0-6 months), once daily, one drop of vehicle solution using a single-use per eye applicator will be applied to the upper eyelid margin (where the eyelashes meet the skin). For treatment period two (6-12 months), once daily, one drop of Bimatoprost 0.03% solution using a single-use per eye applicator will be applied to the upper eyelid margin.
All Cause Mortality
	Bimatoprost 0.03% Followed by Bimatoprost 0.03%		Bimatoprost 0.03% Followed by Vehicle		Vehicle Followed by Bimatoprost 0.03%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bimatoprost 0.03% Followed by Bimatoprost 0.03%		Bimatoprost 0.03% Followed by Vehicle		Vehicle Followed by Bimatoprost 0.03%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/214 (9.3%)		3/60 (5%)		9/92 (9.8%)
Cardiac disorders
Cardiac Arrest	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Gastrointestinal disorders
Gastrointestinal Inflammation	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Retroperitoneal Haematoma	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
General disorders
Chest Pain	0/214 (0%)		1/60 (1.7%)		0/92 (0%)
Infections and infestations
Staphylococcal Infection	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Bronchitis	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Breast Cellulitis	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Pneumonia	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Injury, poisoning and procedural complications
Road Traffic Accident	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Wound	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Wound Dehiscence	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Wrist Fracture	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Seroma	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Musculoskeletal Pain	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer Metastatic	3/214 (1.4%)		0/60 (0%)		0/92 (0%)
Ovarian Cancer	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Thyroid Cancer	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Basal Cell Carcinoma	0/214 (0%)		2/60 (3.3%)		0/92 (0%)
Breast Cancer	0/214 (0%)		0/60 (0%)		2/92 (2.2%)
Lung Carcinoma Cell Type Unspecified Stage IV	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Nervous system disorders
Migraine	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Reproductive system and breast disorders
Ovarian Cyst	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Vaginal Prolapse	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/214 (0.5%)		0/60 (0%)		0/92 (0%)
Asthma	0/214 (0%)		0/60 (0%)		1/92 (1.1%)
Surgical and medical procedures
Breast Reconstruction	1/214 (0.5%)		0/60 (0%)		1/92 (1.1%)
Other (Not Including Serious) Adverse Events
	Bimatoprost 0.03% Followed by Bimatoprost 0.03%		Bimatoprost 0.03% Followed by Vehicle		Vehicle Followed by Bimatoprost 0.03%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/214 (35%)		21/60 (35%)		36/92 (39.1%)
Eye disorders
Conjunctival Hyperaemia	26/214 (12.1%)		4/60 (6.7%)		6/92 (6.5%)
Punctate Keratitis	12/214 (5.6%)		3/60 (5%)		5/92 (5.4%)
Eyelids Pruritus	10/214 (4.7%)		4/60 (6.7%)		5/92 (5.4%)
Erythema of Eyelid	9/214 (4.2%)		6/60 (10%)		5/92 (5.4%)
Infections and infestations
Upper Respiratory Tract Infection	9/214 (4.2%)		0/60 (0%)		5/92 (5.4%)
Nasopharyngitis	5/214 (2.3%)		4/60 (6.7%)		4/92 (4.3%)
Nervous system disorders
Headache	4/214 (1.9%)		0/60 (0%)		6/92 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A 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 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo