An Exploratory Study to Evaluate the Safety of Brimonidine Intravitreal Implant in Patients With Retinitis Pigmentosa

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00661479
• Collaborator: (none)
• Enrollment: 21
• Locations: 4
• Arms: 4
• Duration (Months): 22
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This exploratory, 12-month, ascending-dose study will evaluate the safety and effects on visual function of a single injection of Brimonidine intravitreal implant in one eye of patients with Retinitis Pigmentosa.

Condition or Disease	Intervention/Treatment	Phase
Retinitis Pigmentosa	Drug: 400 µg Brimonidine Tartrate Implant; Drug: 200 µg Brimonidine Tartrate Implant; Drug: 100 µg Brimonidine Tartrate Implant; Other: Sham (no implant)	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 400 µg Brimonidine Tartrate Implant Group B 400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	Drug: 400 µg Brimonidine Tartrate Implant; 400 µg brimonidine tartrate implant in the study eye on Day 1.; Other Names: Brimonidine Tartrate PS DDS® ; Other: Sham (no implant); Sham in the fellow eye on Day 1.
Experimental: 200 µg Brimonidine Tartrate Implant Group B 200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	Drug: 200 µg Brimonidine Tartrate Implant; 200 µg brimonidine tartrate implant in the study eye on Day 1.; Other Names: Brimonidine Tartrate PS DDS® ; Other: Sham (no implant); Sham in the fellow eye on Day 1.
Experimental: 100 µg Brimonidine Tartrate Implant Group B 100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	Drug: 100 µg Brimonidine Tartrate Implant; 100 µg brimonidine tartrate implant in the study eye on Day 1.; Other Names: Brimonidine Tartrate PS DDS® ; Other: Sham (no implant); Sham in the fellow eye on Day 1.
Experimental: 100 µg Brimonidine Tartrate Implant Group A 100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	Drug: 100 µg Brimonidine Tartrate Implant; 100 µg brimonidine tartrate implant in the study eye on Day 1.; Other Names: Brimonidine Tartrate PS DDS® ; Other: Sham (no implant); Sham in the fellow eye on Day 1.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye [Baseline, Month 6]

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.

Secondary Outcome Measures

1. Change From Baseline in Contrast Sensitivity in the Study Eye [Baseline, Month 6]

   Change from baseline in contrast sensitivity in the study eye is measured using a Pelli-Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Retinitis Pigmentosa in both eyes

• Visual acuity between 20/40 to count fingers

Exclusion Criteria:

• Growth of new blood vessels in the eye

• Any intraocular surgery or laser in either eye in the last 6 months prior to Screening visit or between the Screening visit and Day 1

• Any ocular disease that can interfere with diagnosis and or assessment of disease progression

• Significant near-sightedness

• HIV

• Female patients who are pregnant, nursing, or planning pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Arlington	Texas	United States
2		Paris		France
3		Tubingen		Germany
4		Coimbra		Portugal

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: NCT00661479
• Other Study ID Numbers: 190342-028D
• First Posted: Apr 18, 2008
• Last Update Posted: Apr 24, 2013
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Retinitis; Retinitis Pigmentosa; Brimonidine Tartrate

Study Results

Participant Flow

Pre-assignment Detail	Patients were stratified by Best Corrected Visual Acuity (BCVA). Patients assigned to Group A had a BCVA of 20/320. Patients assigned to Group B had a BCVA worse than 20/40 and better than 20/320. Patients in Group A were randomized and treated prior to initiating enrollment in Group B. No patients from Group A participated in Group B.

Arm/Group Title	400 µg Brimonidine Tartrate Implant Group B	200 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group A
Arm/Group Description	400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.
Period Title: Overall Study
STARTED	12	3	3	3
COMPLETED	12	3	3	3
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	400 µg Brimonidine Tartrate Implant Group B	200 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group A	Total
Arm/Group Description	400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	Total of all reporting groups
Overall Participants	12	3	3	3	21
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.3 (18.70)	56.3 (6.03)	48.7 (4.04)	69.0 (5.29)	51.3 (16.36)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	1 33.3%	3 100%	0 0%	9 42.9%
Male	7 58.3%	2 66.7%	0 0%	3 100%	12 57.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

Safety Population: all patients treated on Day 1

Arm/Group Title	400 µg Brimonidine Tartrate Implant Group B	200 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group A
Arm/Group Description	400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.
Measure Participants	12	3	3	3
Baseline	48.5 (14.61)	51.0 (14.18)	52.7 (3.79)	4.0 (3.46)
Change from Baseline at Month 6	3.2 (4.41)	-1.3 (4.04)	3.3 (8.50)	0.3 (3.79)

2. Secondary Outcome

Title	Change From Baseline in Contrast Sensitivity in the Study Eye
Description	Change from baseline in contrast sensitivity in the study eye is measured using a Pelli-Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

Safety Population: all patients treated on Day 1

Arm/Group Title	400 µg Brimonidine Tartrate Implant Group B	200 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group B	100 µg Brimonidine Tartrate Implant Group A
Arm/Group Description	400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.	100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.
Measure Participants	12	3	3	3
Baseline	15.5 (8.48)	18.0 (7.21)	22.3 (1.53)	3.0 (3.46)
Change from Baseline at Month 6	0.8 (4.86)	-0.3 (5.86)	4.3 (1.15)	-2.0 (1.73)

Adverse Events

Adverse Event Reporting Description	For Ocular AEs, only those occurring in the study eye are reported in the "Other Adverse Events" section. For SAEs, all ocular events were reported, regardless of eye.
Arm/Group Title	400 µg Brimonidine Tartrate Implant Group B		200 µg Brimonidine Tartrate Implant Group B		100 µg Brimonidine Tartrate Implant Groups A and B
Arm/Group Description	400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.		200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.		100 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1.
All Cause Mortality
	400 µg Brimonidine Tartrate Implant Group B		200 µg Brimonidine Tartrate Implant Group B		100 µg Brimonidine Tartrate Implant Groups A and B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	400 µg Brimonidine Tartrate Implant Group B		200 µg Brimonidine Tartrate Implant Group B		100 µg Brimonidine Tartrate Implant Groups A and B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/3 (0%)		1/6 (16.7%)
Nervous system disorders
Syncope	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Myelitis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	400 µg Brimonidine Tartrate Implant Group B		200 µg Brimonidine Tartrate Implant Group B		100 µg Brimonidine Tartrate Implant Groups A and B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		3/3 (100%)		6/6 (100%)
Congenital, familial and genetic disorders
Colour Blindness	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Ear and labyrinth disorders
Tinnitus	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Ear Pain	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Eye disorders
Conjunctival Haemorrhage	5/12 (41.7%)		2/3 (66.7%)		1/6 (16.7%)
Conjunctival Hyperaemia	5/12 (41.7%)		3/3 (100%)		5/6 (83.3%)
Foreign Body Sensation in Eyes	3/12 (25%)		0/3 (0%)		1/6 (16.7%)
Ocular Discomfort	3/12 (25%)		0/3 (0%)		1/6 (16.7%)
Glare	2/12 (16.7%)		0/3 (0%)		0/6 (0%)
Eye Pain	2/12 (16.7%)		0/3 (0%)		2/6 (33.3%)
Conjunctival Oedema	2/12 (16.7%)		2/3 (66.7%)		1/6 (16.7%)
Conjunctivitis Allergic	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Dry Eye	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Eye Irritation	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Lacrimation Increased	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Vision Blurred	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Visual Disturbance	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Abnormal Sensation in Eye	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Keratitis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Visual Acuity Reduced	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Vitreous Floaters	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Conjunctivitis	0/12 (0%)		1/3 (33.3%)		0/6 (0%)
Gastrointestinal disorders
Nausea	2/12 (16.7%)		0/3 (0%)		0/6 (0%)
Abdominal pain	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Abdominal Pain Upper	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Gastritis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Dental Caries	0/12 (0%)		1/3 (33.3%)		0/6 (0%)
General disorders
Fatigue	2/12 (16.7%)		0/3 (0%)		0/6 (0%)
Influenza Like Illness	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Infections and infestations
Nasopharyngitis	3/12 (25%)		0/3 (0%)		2/6 (33.3%)
Rhinitis	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Bacteriuria	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Bronchitis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Prostate Infection	0/7 (0%)		0/2 (0%)		1/3 (33.3%)
Urinary Tract Infection	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Pharyngitis	0/12 (0%)		1/3 (33.3%)		0/6 (0%)
Injury, poisoning and procedural complications
Bite	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Foot Fracture	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Ligament Injury	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Wound	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Renal Injury	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Dehydration	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Muscle Contracture	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Osteoarthritis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Tendonitis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Headache	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Neuropathy Peripheral	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Syncope	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Myelitis	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Restless Legs Syndrome	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Psychiatric disorders
Anxiety	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Insomnia	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Reproductive system and breast disorders
Epididymitis	1/7 (14.3%)		0/2 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Rhinitis Allergic	0/12 (0%)		0/3 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Dermatitis Allergic	1/12 (8.3%)		0/3 (0%)		0/6 (0%)
Vascular disorders
Orthostatic Hypotension	1/12 (8.3%)		0/3 (0%)		0/6 (0%)

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.