Long-Term Safety of Bimatoprost Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01298700
• Collaborator: (none)
• Enrollment: 806
• Locations: 50
• Arms: 2
• Actual Duration (Months): 66.2
• Patients Per Site: 16.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the long-term safety of bimatoprost 0.01% ophthalmic solution compared with bimatoprost 0.03% ophthalmic solution in patients with glaucoma or ocular hypertension.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma; Ocular Hypertension	Drug: bimatoprost 0.01% ophthalmic solution; Drug: bimatoprost 0.03% ophthalmic solution	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 806 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 2-year, Multicenter, Double-masked, Randomized, Parallel Study of the Safety of LUMIGAN® 0.1 mg/mL Compared With LUMIGAN® 0.3 mg/mL in Patients With Glaucoma or Ocular Hypertension
• Actual Study Start Date: May 31, 2011
• Actual Primary Completion Date: Dec 6, 2016
• Actual Study Completion Date: Dec 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bimatoprost 0.01% Ophthalmic Solution One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	Drug: bimatoprost 0.01% ophthalmic solution; One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.; Other Names: LUMIGAN® 0.01% LUMIGAN 0.1 mg/ml
Active Comparator: Bimatoprost 0.03% Ophthalmic Solution One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	Drug: bimatoprost 0.03% ophthalmic solution; One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.; Other Names: LUMIGAN® 0.03% LUMIGAN 0.3 mg/ml

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Reporting One or More Treatment-Related Ocular Surface Adverse Events [24 Months]

   An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The percentage of participants with ocular (eye) surface AEs deemed related to treatment by the investigator are reported.

Secondary Outcome Measures

1. Percentage of Participants Reporting One or More Treatment-Related Ocular Surface Adverse Events Excluding "Conjunctival Hyperemia" [24 Months]

   An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The percentage of participants with ocular (eye) surface AEs deemed related to treatment by the investigator excluding AEs with the preferred term Conjunctival hyperemia are reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ocular hypertension or glaucoma in each eye

• Requires intraocular pressure (IOP)-lowering therapy in both eyes

• Best corrected visual acuity of 20/100 or better in each eye

Exclusion Criteria:

• Ocular seasonal allergies within 2 years

• Required chronic use of ocular medications during the study (intermittent use of artificial tears is allowed)

• Ocular surgery or laser within 3 months

• Anticipated wearing of contact lenses during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZ Leuven	Leuven		Belgium	3000
2	CHU Sart Tilman	Liege		Belgium	4000
3	University Hospital Brno	Brno		Czechia	62500
4	Eye Clinic	Frydstejn		Czechia	463 42
5	Centre Hospitalier Universitaire de Bordeaux	Bordeaux		France	33076
6	Clinique Montcelli	Marseille		France	13008
7	Universitat Augenklinik	Freiburg		Germany	79106
8	Univ. des Saarlandes	Homburg Saar		Germany	66421
9	Johannes Gutenberg Univ Mainz	Mainz		Germany	55131
10	Thelen Private Practice	Műnster		Germany	48143
11	Augenzentrum Siegburg	Siegburg		Germany	53721
12	Department of Ophthalmology, University of Tuebingen	Tubingen		Germany	72076
13	Budapest Retina Associates Kft.	Budapest		Hungary	H-1133
14	University Med. School of Debrecen	Debrecen		Hungary	H-4032
15	Josa Andras Oktatokorhaz	Nyíregyháza		Hungary	H-4400
16	University of Szeged Szent-Gyorgyi Albert Clinical Center	Szeged		Hungary	H-6720
17	Carmel Medical Center	Haifa		Israel	34362
18	Glaucoma Service The Rabin Medical Center	Petach Tiqva		Israel	49100
19	Kaplan Medical Center	Rehovot		Israel	76100
20	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
21	Sheba Medical Center	Tel-Hashomer		Israel	52621
22	Azienda Ospedaliera Universitaria	Catania		Italy	95123
23	Azlenda Ospedaliero Universitaria Careggi Viale	Firenze		Italy	50134
24	Istituto Scientifico San Raffaele	Milano		Italy	20132
25	Dipartimento di Scienze Otorino-Odonto-Oftalmologiche e Cerv	Parma		Italy	43126
26	Fondazione G.B. Bietti per l'Oftalmologia I.R.C.C.S.	Rome		Italy	00198
27	EuroMedic Kliniki Specjalistyczne	Katowice		Poland	40-519
28	ZOZ OKO- TEST Poradnia Okulistyczna	Nowy Targ		Poland	34-400
29	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu	Poznan		Poland	61-848
30	Samodzielny Publiczny Szpital	Szczecin		Poland	70-111
31	Osrodek Badan Klinicznych Euromedis Sp. z o.o.	Szczecin		Poland	70-215
32	Samodzielny Szpital Kliniczny	Warszawa		Poland	00-416
33	Akad. Med. w Warszawie - Ketedra I Klin. Okulistki Wyzialu L	Warszawa		Poland	03-709
34	Centro de Ojos de La Coruña	A Coruña		Spain	15006
35	Hospital de Torrevieja	Alicante		Spain	03018
36	Instituro Condal de Oftalmologia	Barcelona		Spain	08006
37	Hospital Quiron Barcelona	Barcelona		Spain	08023
38	Valles Oftalmologia Recerca	Barcelona		Spain	08195
39	Hospital Ramon y Cajal	Madrid		Spain	28034
40	Hospital Universitario La Paz	Madrid		Spain	28046
41	Instituto oftalmologico Fernandez Vega	Oviedo		Spain	33012
42	Fundacion Oftalmologica Del Mediterraneo	Valencia		Spain	46015
43	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
44	Birmingham & Midland Eye Center	Birmingham		United Kingdom	B18 7QH
45	Huntingdon Glaucoma Diagnostic & Research Centre	Huntingdon		United Kingdom	PE29 6NT
46	Western Eye Hospital	London		United Kingdom	NW1 5YE
47	St Thomas' Hospital	London		United Kingdom	SE1 7EH
48	Norfolk and Norwich Hospital	Norwich		United Kingdom	NR1 3SR
49	University Hospital Nottingham	Nottingham		United Kingdom	NG7 2UH
50	Southampton General Hospital	Southampton		United Kingdom	S016 6YD

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Kristopher Hansen, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01298700
• Other Study ID Numbers: 192024-054; 2010-023917-68
• First Posted: Feb 18, 2011
• Last Update Posted: Sep 17, 2018
• Last Verified: Dec 1, 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glaucoma; Ocular Hypertension; Hypertension; Bimatoprost; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Bimatoprost 0.01% Ophthalmic Solution	Bimatoprost 0.03% Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.
Period Title: Overall Study
STARTED	403	403
Safety Population: Received Study Drug	400	398
COMPLETED	302	303
NOT COMPLETED	101	100

Baseline Characteristics

Arm/Group Title	Bimatoprost 0.01% Ophthalmic Solution	Bimatoprost 0.03% Ophthalmic Solution	Total
Arm/Group Description	One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	Total of all reporting groups
Overall Participants	400	398	798
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (11.0)	62.2 (11.5)	62.4 (11.3)
Age, Customized (participants) [Number]
< 45 years	22 5.5%	26 6.5%	48 6%
≥ 45 years to ≤ 65 years	216 54%	211 53%	427 53.5%
> 65 years	162 40.5%	161 40.5%	323 40.5%
Sex: Female, Male (Count of Participants)
Female	197 49.3%	187 47%	384 48.1%
Male	203 50.8%	211 53%	414 51.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Reporting One or More Treatment-Related Ocular Surface Adverse Events
Description	An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The percentage of participants with ocular (eye) surface AEs deemed related to treatment by the investigator are reported.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose of study drug.

Arm/Group Title	Bimatoprost 0.01% Ophthalmic Solution	Bimatoprost 0.03% Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.
Measure Participants	400	398
Number [percentage of participants]	33.3 8.3%	37.7 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bimatoprost 0.01% Ophthalmic Solution, Bimatoprost 0.03% Ophthalmic Solution
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.148
	Comments	P-value was stratified by baseline prostaglandin analogue (PGA) treatment(yes/no) and by baseline active ocular surface finding (present/absent).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -11 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	bimatoprost 0.01% ophthalmic solution - bimatoprost 0.03% ophthalmic solution

2. Secondary Outcome

Title	Percentage of Participants Reporting One or More Treatment-Related Ocular Surface Adverse Events Excluding "Conjunctival Hyperemia"
Description	An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The percentage of participants with ocular (eye) surface AEs deemed related to treatment by the investigator excluding AEs with the preferred term Conjunctival hyperemia are reported.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose of study drug.

Arm/Group Title	Bimatoprost 0.01% Ophthalmic Solution	Bimatoprost 0.03% Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.	One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.
Measure Participants	400	398
Number [percentage of participants]	26.0 6.5%	29.6 7.4%

Adverse Events

Time Frame	24 Months
Adverse Event Reporting Description	Safety Population, all participants who received at least one dose of study drug, was used to determine the number of participants at risk for Serious and Non-serious Adverse Events.
Arm/Group Title	Bimatoprost 0.01% Ophthalmic Solution		Bimatoprost 0.03% Ophthalmic Solution
Arm/Group Description	One drop of bimatoprost 0.01% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.		One drop of bimatoprost 0.03% ophthalmic solution instilled to each eye, once daily in the evening for 2 years.
All Cause Mortality
	Bimatoprost 0.01% Ophthalmic Solution		Bimatoprost 0.03% Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bimatoprost 0.01% Ophthalmic Solution		Bimatoprost 0.03% Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/400 (11.3%)		40/398 (10.1%)
Blood and lymphatic system disorders
Anaemia	1/400 (0.3%)		1/398 (0.3%)
Febrile neutropenia	0/400 (0%)		1/398 (0.3%)
Cardiac disorders
Acute myocardial infarction	2/400 (0.5%)		0/398 (0%)
Angina pectoris	2/400 (0.5%)		0/398 (0%)
Acute coronary syndrome	1/400 (0.3%)		0/398 (0%)
Coronary artery thrombosis	1/400 (0.3%)		0/398 (0%)
Myocardial infarction	1/400 (0.3%)		0/398 (0%)
Coronary artery disease	0/400 (0%)		1/398 (0.3%)
Eye disorders
Cataract	2/400 (0.5%)		1/398 (0.3%)
Angle closure glaucoma	1/400 (0.3%)		0/398 (0%)
Cataract cortical	1/400 (0.3%)		0/398 (0%)
Macular hole	1/400 (0.3%)		0/398 (0%)
Retinal detachment	1/400 (0.3%)		0/398 (0%)
Vitreous adhesions	1/400 (0.3%)		0/398 (0%)
Glaucoma	0/400 (0%)		1/398 (0.3%)
Optic neuropathy	0/400 (0%)		1/398 (0.3%)
Gastrointestinal disorders
Anal haemorrhage	1/400 (0.3%)		0/398 (0%)
Inguinal hernia	1/400 (0.3%)		0/398 (0%)
Retroperitoneal haematoma	1/400 (0.3%)		0/398 (0%)
Gastritis	0/400 (0%)		2/398 (0.5%)
Barrett's oesophagus	0/400 (0%)		1/398 (0.3%)
Inguinal hernia repair	0/400 (0%)		1/398 (0.3%)
Intestinal perforation	0/400 (0%)		1/398 (0.3%)
Large intestine polyp	0/400 (0%)		1/398 (0.3%)
Pancreatitis relapsing	0/400 (0%)		1/398 (0.3%)
Peritoneal haematoma	0/400 (0%)		1/398 (0.3%)
General disorders
Pyrexia	1/400 (0.3%)		0/398 (0%)
Catheter site inflammation	0/400 (0%)		1/398 (0.3%)
Non-cardiac chest pain	0/400 (0%)		1/398 (0.3%)
Hepatobiliary disorders
Cholecystitis	1/400 (0.3%)		0/398 (0%)
Hepatic cirrhosis	1/400 (0.3%)		0/398 (0%)
Hepatitis acute	1/400 (0.3%)		0/398 (0%)
Cholelithiasis	0/400 (0%)		2/398 (0.5%)
Cholecystitis acute	0/400 (0%)		1/398 (0.3%)
Infections and infestations
Anal abscess	1/400 (0.3%)		0/398 (0%)
Peritonsillar abscess	1/400 (0.3%)		0/398 (0%)
Pneumonia	1/400 (0.3%)		0/398 (0%)
Wound infection	1/400 (0.3%)		0/398 (0%)
Bronchitis	0/400 (0%)		1/398 (0.3%)
Echinococciasis	0/400 (0%)		1/398 (0.3%)
Gastroenteritis	0/400 (0%)		1/398 (0.3%)
Vestibular neuronitis	0/400 (0%)		1/398 (0.3%)
Injury, poisoning and procedural complications
Ankle fracture	1/400 (0.3%)		0/398 (0%)
Clavicle fracture	1/400 (0.3%)		0/398 (0%)
Fall	1/400 (0.3%)		0/398 (0%)
Humerus fracture	1/400 (0.3%)		0/398 (0%)
Limb crushing injury	1/400 (0.3%)		0/398 (0%)
Lumbar vertebral fracture	1/400 (0.3%)		0/398 (0%)
Pelvic fracture	1/400 (0.3%)		0/398 (0%)
Pulmonary contusion	1/400 (0.3%)		0/398 (0%)
Rib fracture	1/400 (0.3%)		0/398 (0%)
Subarachnoid haemorrhage	1/400 (0.3%)		0/398 (0%)
Upper limb fracture	1/400 (0.3%)		0/398 (0%)
Foot fracture	0/400 (0%)		1/398 (0.3%)
Joint dislocation	0/400 (0%)		1/398 (0.3%)
Radius fracture	0/400 (0%)		1/398 (0.3%)
Tendon rupture	0/400 (0%)		1/398 (0.3%)
Urostomy complication	0/400 (0%)		1/398 (0.3%)
Wrist fracture	0/400 (0%)		1/398 (0.3%)
Investigations
Intraocular pressure fluctuation	4/400 (1%)		2/398 (0.5%)
Intraocular pressure increased	1/400 (0.3%)		1/398 (0.3%)
Metabolism and nutrition disorders
Hypocalcaemia	1/400 (0.3%)		0/398 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/400 (0.3%)		1/398 (0.3%)
Lumbar spinal stenosis	1/400 (0.3%)		0/398 (0%)
Spinal disorder	1/400 (0.3%)		0/398 (0%)
Arthropathy	0/400 (0%)		1/398 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/400 (0.3%)		1/398 (0.3%)
Hodgkin's disease	1/400 (0.3%)		0/398 (0%)
Laryngeal squamous cell carcinoma	1/400 (0.3%)		0/398 (0%)
Lip squamous cell carcinoma	1/400 (0.3%)		0/398 (0%)
Malignant melanoma	1/400 (0.3%)		0/398 (0%)
Meningioma benign	1/400 (0.3%)		0/398 (0%)
Pancreatic carcinoma	1/400 (0.3%)		0/398 (0%)
Renal cancer	1/400 (0.3%)		0/398 (0%)
Tubular breast carcinoma	1/400 (0.3%)		0/398 (0%)
Basal cell carcinoma	0/400 (0%)		1/398 (0.3%)
Breast cancer metastatic	0/400 (0%)		1/398 (0.3%)
Gastric cancer	0/400 (0%)		1/398 (0.3%)
Metastases to central nervous system	0/400 (0%)		1/398 (0.3%)
Metastases to lung	0/400 (0%)		1/398 (0.3%)
Oesophageal carcinoma	0/400 (0%)		1/398 (0.3%)
Nervous system disorders
Cerebrovascular accident	2/400 (0.5%)		1/398 (0.3%)
Cervical radiculopathy	1/400 (0.3%)		0/398 (0%)
Hydrocephalus	1/400 (0.3%)		0/398 (0%)
Haemorrhage intracranial	0/400 (0%)		1/398 (0.3%)
Headache	0/400 (0%)		1/398 (0.3%)
Partial seizures	0/400 (0%)		1/398 (0.3%)
Psychiatric disorders
Completed suicide	1/400 (0.3%)		0/398 (0%)
Renal and urinary disorders
Nephrotic syndrome	0/400 (0%)		1/398 (0.3%)
Urinary retention	0/400 (0%)		1/398 (0.3%)
Bladder prolapse	1/400 (0.3%)		0/398 (0%)
Reproductive system and breast disorders
Vaginal prolapse	1/197 (0.5%)		0/187 (0%)
Benign prostatic hyperplasia	0/203 (0%)		1/211 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/400 (0.3%)		0/398 (0%)
Acute pulmonary oedema	0/400 (0%)		1/398 (0.3%)
Sleep apnoea syndrome	0/400 (0%)		1/398 (0.3%)
Surgical and medical procedures
Inguinal hernia repair	0/400 (0%)		1/398 (0.3%)
Vascular disorders
Arteriosclerosis	1/400 (0.3%)		0/398 (0%)
Hypotension	1/400 (0.3%)		0/398 (0%)
Other (Not Including Serious) Adverse Events
	Bimatoprost 0.01% Ophthalmic Solution		Bimatoprost 0.03% Ophthalmic Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	167/400 (41.8%)		186/398 (46.7%)
Eye disorders
Blepharitis	14/400 (3.5%)		23/398 (5.8%)
Cataract	20/400 (5%)		24/398 (6%)
Conjunctival hyperaemia	80/400 (20%)		90/398 (22.6%)
Dry eye	36/400 (9%)		42/398 (10.6%)
Eye pain	21/400 (5.3%)		20/398 (5%)
Foreign body sensation in eyes	11/400 (2.8%)		21/398 (5.3%)
Punctate keratitis	22/400 (5.5%)		30/398 (7.5%)
Infections and infestations
Influenza	26/400 (6.5%)		21/398 (5.3%)

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.