Clinical Endpoint Study of Nepafenac 0.3% Opthalmic Suspension

• Sponsor: Actavis Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03499873
• Collaborator: (none)
• Enrollment: 448
• Location: 1
• Arms: 3
• Actual Duration (Months): 8.7
• Patients Per Site Per Month: 51.5

Study Details

Study Description

Brief Summary

A randomized, multicenter, double masked, placebo controlled, parallel group, bioequivalence study to evaluate the clinical equivalence and safety of Nepafenac 0.3% ophthalmic suspension (manufactured by Indoco remedies Ltd. for Actavis LLC) with IlevroTM (Nepafenac ophthalmic suspension), 0.3% of Alcon Laboratories, Inc. for the treatment of pain and inflammation associated with cataract surgery.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Drug: Nepafenac 0.3% Oph Susp; Drug: Placebos; Drug: Nepafenac 0.3% Oph Susp (reference)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 448 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double Masked, Placebo Controlled, Parallel Group, Bioequivalence Study to Evaluate the Clinical Equivalence and Safety of Nepafenac 0.3% Ophthalmic Suspension (Manufactured by Indoco Remedies Ltd. for Actavis LLC) With IlevroTM (Nepafenac Ophthalmic Suspension), 0.3% of Alcon Laboratories, Inc. for the Treatment of Pain and Inflammation Associated With Cataract Surgery.
• Actual Study Start Date: Mar 28, 2018
• Actual Primary Completion Date: Oct 31, 2018
• Actual Study Completion Date: Dec 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nepafenac 0.3% Opthalmic Suspension Test product manufactured by Indoco Remedies, Ltd for Actavis LLC.	Drug: Nepafenac 0.3% Oph Susp; Nepafenac 0.3% Ophthalmic suspension (experimental product)
Active Comparator: Ilevro 0.3% Opthalmic Suspension Reference product manufactured by Alcon Laboratories Inc.	Drug: Nepafenac 0.3% Oph Susp (reference); Nepafenac 0.3% Ophthalmic suspension (Innovator)
Placebo Comparator: Placebo (vehicle) Opthalmic Suspension Placebo (vehicle) manufactured by Indoco Remedies, Ltd for Actavis LLC.	Drug: Placebos; Placebo

Outcome Measures

Primary Outcome Measures

1. Cure at Day 14 [14 days]

   Number of participants that achieved cure at Day 14 defined as a score of 0 for aqueous cells (Grade 0-4 using a narrow-slit beam (0.5 mm width at least 8 mm length) at maximum luminance), a score of 0 for aqueous flare (Grade 0-3 using a narrow-slit beam (0.5 mm width at least 8 mm length) at maximum luminance) and a score of no more than 3 for pain (Grade 0-5 a positive sensation of the eye, including foreign body sensation, stabbing, throbbing or aching). The scoring indicates from less severe at 0 to very severe as the grading increases.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Males or non-pregnant, non-lactating females, 18 years of age or older who have a cataract and are expected to undergo cataract extraction.

2. No aqueous cells, no visible aqueous flare and no significant ocular pain in the selected eye noted during the Screening visit by slit-lamp examination.

3. Study subjects must have provided IRB approved written informed consent using the latest version of the IRB informed consent form. In addition, study subjects must sign a HIPAA authorization, if applicable.

4. Study subjects should be literate and willing to complete the subject diary regularly as directed.

5. Study subjects must be in good health and free from any clinically significant disease apart from indication under study.

6. Females of child bearing potential (WOCBP*) must not be pregnant or lactating at baseline visit (as documented by a negative urine pregnancy test with a minimum sensitivity of 25 IU/L or equivalent units of beta-human chorionic gonadotropin (Beta-HCG) at screening and urine pregnancy at baseline.

7. Female subjects of childbearing potential must be willing to use an acceptable form of birth control from the day of the first dose administration to 30 days after the last administration of IP. For the purpose of this study the following are considered acceptable methods of birth control: oral or injectable contraceptives, contraceptive patches, Depo-Provera® (Medroxyprogesterone acetate-stabilized for at least 3 months); vaginal contraceptive; contraceptive implant; double barrier methods (e.g. condom and spermicide); Nuvaring vaginal hormonal birth control, IUD, or abstinence with a second method of birth control should the subject become sexually active. A sterile sexual partner is NOT considered an adequate form of birth control.

8. All male subjects must agree to use accepted methods of birth control with their partners, from the day of the first dose administration (to 30 days after the last administration of study drug). Please see acceptable forms for "Female" birth control above. Abstinence is an acceptable method of birth control for males.

9. Study subjects must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required scheduled study visits.

10. Study subjects must be willing to refrain from using any other treatments other than the investigational product.

Exclusion Criteria:

1. Females who are pregnant, breast feeding, or planning a pregnancy during the course of the study and for 30 days after last study dose.

2. Females of childbearing potential who do not agree to utilize an adequate form of contraception.

3. Current or past history of severe hepatic or renal impairment, uncontrolled diabetes mellitus, rheumatoid arthritis or bleeding tendencies.

4. Current or history within two months prior to baseline of clinically significant ocular disease, e.g., corneal denervation, corneal epithelial defects, severe dry eye syndrome, ocular trauma to the operative eye, corneal edema, proliferative diabetic retinopathy in the operative eye or ocular infection.

5. In the operative eye, history of chronic or recurrent inflammatory disease, e.g., iritis, scleritis, uveitis, iridocyclitis or rubeosis iritis, lens pseudoexfoliation syndrome with glaucoma or zonular compromise.

6. Congenital ocular anomaly, e.g., aniridia or congenital cataract.

7. Iris atrophy in the operative eye.

8. Current corneal abnormalities that would prevent accurate IOP readings with the Goldmann applanation tonometer.

9. Nonfunctional nonoperative eye (visual acuity of 20/200 or worse Snellen or ETDRS).

10. Known hypersensitivity to any component of nepafenac therapy or to other nonsteroidal anti-inflammatory drug (NSAID).

11. Use within one week prior to baseline of: 1) contact lens, or 2) topical, ophthalmic or systemic NSAID.

12. Use within two weeks prior to baseline of: 1) topical ophthalmic corticosteroid, 2) topical corticosteroid, or 3) medications which may prolong bleeding time (per investigator discretion and primary care physician approval to discontinue use for surgery).

13. Use within one month prior to baseline of: 1) systemic corticosteroid, 2) high-dose salicylate therapy, or 3) topical ophthalmic prostaglandin analogs, e.g., bimatoprost, latanoprost or travoprost.

14. Use within six months prior to baseline of intravitreal or subtenon injection of ophthalmic corticosteroid.

15. Underwent within six months prior to baseline any complicated intraocular surgery or repeat ocular surgeries (e.g., cataract surgery).

16. Underwent within twelve months prior to baseline: refractive surgery, filtering surgery or laser surgery for IOP reduction.

17. History or presence of significant alcoholism or drug abuse in the past one year.

18. History or presence of significant smoking (more than 20 cigarettes or any other equivalent tobacco product/day).

19. History of hematologic disorders other than mild anemia.

20. Severe, unstable, or uncontrolled cardiovascular or pulmonary disease.

21. Therapy with an investigational agent within the past 30 days prior to screening.

22. Clinically significant hematologic and / or biochemical abnormalities based on laboratory testing.

23. Subjects who are in the investigator's best judgment at risk of visual field or visual acuity worsening as a consequence of participation in trial.

24. Use of any prescribed medication during last two weeks or OTC medicinal products during the last one week preceding the first dosing that results in drug-drug interaction with the study drug.

25. Major illness, as per investigator discretion, during 3 months before screening.

26. Subjects who are employees of site or CRO or sponsor or immediate family of employees.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Key-Whitman Eye Center	Dallas	Texas	United States	75243

Sponsors and Collaborators

• Actavis Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 25, 2018
• Statistical Analysis Plan - Sep 11, 2018

More Information

Publications

None provided.

• Responsible Party: Actavis Inc.
• ClinicalTrials.gov Identifier: NCT03499873
• Other Study ID Numbers: TCTM/NEPA/2017
• First Posted: Apr 17, 2018
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Cataract; Nepafenac

Study Results

Participant Flow

Arm/Group Title	Nepafenac 0.3% Opthalmic Suspension	Ilevro 0.3% Opthalmic Suspension	Placebo (Vehicle) Opthalmic Suspension
Arm/Group Description	Test product manufactured by Indoco Remedies, Ltd for Actavis LLC. Nepafenac 0.3% Oph Susp: Nepafenac 0.3% Ophthalmic suspension (experimental product)	Reference product manufactured by Alcon Laboratories Inc. Nepafenac 0.3% Oph Susp (reference): Nepafenac 0.3% Ophthalmic suspension (Innovator)	Placebo (vehicle) manufactured by Indoco Remedies, Ltd for Actavis LLC. Placebos: Placebo
Period Title: Overall Study
STARTED	183	182	83
Safety Population	175	174	80
Per-Protocol Population	144	143	58
Modified-Intent-to-Treat	170	168	77
COMPLETED	163	162	56
NOT COMPLETED	20	20	27

Baseline Characteristics

Arm/Group Title	Nepafenac 0.3% Opthalmic Suspension	Ilevro 0.3% Opthalmic Suspension	Placebo (Vehicle) Opthalmic Suspension	Total
Arm/Group Description	Test product manufactured by Indoco Remedies, Ltd for Actavis LLC. Nepafenac 0.3% Oph Susp: Nepafenac 0.3% Ophthalmic suspension (experimental product)	Reference product manufactured by Alcon Laboratories Inc. Nepafenac 0.3% Oph Susp (reference): Nepafenac 0.3% Ophthalmic suspension (Innovator)	Placebo (vehicle) manufactured by Indoco Remedies, Ltd for Actavis LLC. Placebos: Placebo	Total of all reporting groups
Overall Participants	175	174	80	429
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.1 (8.73)	68.5 (9.12)	67.0 (10.19)	68.1 (9.17)
Sex: Female, Male (Count of Participants)
Female	113 64.6%	89 51.1%	47 58.8%	249 58%
Male	62 35.4%	85 48.9%	33 41.3%	180 42%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	50 28.6%	42 24.1%	21 26.3%	113 26.3%
Not Hispanic or Latino	117 66.9%	120 69%	52 65%	289 67.4%
Unknown or Not Reported	8 4.6%	12 6.9%	7 8.8%	27 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%	1 0.6%	0 0%	2 0.5%
Asian	8 4.6%	3 1.7%	2 2.5%	13 3%
Native Hawaiian or Other Pacific Islander	2 1.1%	1 0.6%	1 1.3%	4 0.9%
Black or African American	24 13.7%	24 13.8%	13 16.3%	61 14.2%
White	117 66.9%	122 70.1%	56 70%	295 68.8%
More than one race	1 0.6%	0 0%	0 0%	1 0.2%
Unknown or Not Reported	22 12.6%	23 13.2%	8 10%	53 12.4%
Iris Colour (Count of Participants)
Blue	38 21.7%	47 27%	13 16.3%	98 22.8%
Green	8 4.6%	11 6.3%	9 11.3%	28 6.5%
Grey	2 1.1%	1 0.6%	2 2.5%	5 1.2%
Hazel	19 10.9%	21 12.1%	9 11.3%	49 11.4%
Brown	97 55.4%	81 46.6%	41 51.3%	219 51%
Black	11 6.3%	13 7.5%	6 7.5%	30 7%
Baseline Ocular Pain Grade in Study Eye (Count of Participants)
Grade 0 (less severe)	172 98.3%	172 98.9%	80 100%	424 98.8%
Grade 1	1 0.6%	1 0.6%	0 0%	2 0.5%
Grade 2	0 0%	0 0%	0 0%	0 0%
Grade 3	0 0%	0 0%	0 0%	0 0%
Grade 4	0 0%	0 0%	0 0%	0 0%
Grade 5 (most severe)	0 0%	0 0%	0 0%	0 0%
Missing	2 1.1%	1 0.6%	0 0%	3 0.7%
Baseline Aqueous Cells Grade in Study Eye (Count of Participants)
Grade 0 (least severe)	173 98.9%	173 99.4%	80 100%	426 99.3%
Grade 1	0 0%	0 0%	0 0%	0 0%
Grade 2	0 0%	0 0%	0 0%	0 0%
Grade 3	0 0%	0 0%	0 0%	0 0%
Grade 4 (most severe)	0 0%	0 0%	0 0%	0 0%
Missing	2 1.1%	1 0.6%	0 0%	3 0.7%
Baseline Aqueous Flare Grade in Study Eye (Count of Participants)
Grade 0 (least severe)	173 98.9%	173 99.4%	80 100%	426 99.3%
Grade 1	0 0%	0 0%	0 0%	0 0%
Grade 2	0 0%	0 0%	0 0%	0 0%
Grade 3 (most severe)	0 0%	0 0%	0 0%	0 0%
Missing	2 1.1%	1 0.6%	0 0%	3 0.7%

Outcome Measures

1. Primary Outcome

Title	Cure at Day 14
Description	Number of participants that achieved cure at Day 14 defined as a score of 0 for aqueous cells (Grade 0-4 using a narrow-slit beam (0.5 mm width at least 8 mm length) at maximum luminance), a score of 0 for aqueous flare (Grade 0-3 using a narrow-slit beam (0.5 mm width at least 8 mm length) at maximum luminance) and a score of no more than 3 for pain (Grade 0-5 a positive sensation of the eye, including foreign body sensation, stabbing, throbbing or aching). The scoring indicates from less severe at 0 to very severe as the grading increases.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Per-Protocol Population

Arm/Group Title	Nepafenac 0.3% Opthalmic Suspension	Ilevro 0.3% Opthalmic Suspension	Placebo (Vehicle) Opthalmic Suspension
Arm/Group Description	Test product manufactured by Indoco Remedies, Ltd for Actavis LLC. Nepafenac 0.3% Oph Susp: Nepafenac 0.3% Ophthalmic suspension (experimental product)	Reference product manufactured by Alcon Laboratories Inc. Nepafenac 0.3% Oph Susp (reference): Nepafenac 0.3% Ophthalmic suspension (Innovator)	Placebo (vehicle) manufactured by Indoco Remedies, Ltd for Actavis LLC. Placebos: Placebo
Measure Participants	144	143	58
Cure	94 53.7%	97 55.7%	24 30%
Failure	50 28.6%	46 26.4%	34 42.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nepafenac 0.3% Opthalmic Suspension, Ilevro 0.3% Opthalmic Suspension
	Comments
	Type of Statistical Test	Equivalence
	Comments	90% CI on the Test-to-Reference difference for the proportion of subjects with cure should be contained within the interval [-0.20, +0.20]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.026
	Confidence Interval	(2-Sided) 90%; -0.124 to 0.073
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nepafenac 0.3% Opthalmic Suspension, Placebo (Vehicle) Opthalmic Suspension
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ilevro 0.3% Opthalmic Suspension, Placebo (Vehicle) Opthalmic Suspension
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	1 month
Arm/Group Title	Nepafenac 0.3% Opthalmic Suspension		Ilevro 0.3% Opthalmic Suspension		Placebo (Vehicle) Opthalmic Suspension
Arm/Group Description	Test product manufactured by Indoco Remedies, Ltd for Actavis LLC. Nepafenac 0.3% Oph Susp: Nepafenac 0.3% Ophthalmic suspension (experimental product)		Reference product manufactured by Alcon Laboratories Inc. Nepafenac 0.3% Oph Susp (reference): Nepafenac 0.3% Ophthalmic suspension (Innovator)		Placebo (vehicle) manufactured by Indoco Remedies, Ltd for Actavis LLC. Placebos: Placebo
All Cause Mortality
	Nepafenac 0.3% Opthalmic Suspension		Ilevro 0.3% Opthalmic Suspension		Placebo (Vehicle) Opthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/175 (0%)		0/174 (0%)		0/80 (0%)
Serious Adverse Events
	Nepafenac 0.3% Opthalmic Suspension		Ilevro 0.3% Opthalmic Suspension		Placebo (Vehicle) Opthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/175 (0%)		0/174 (0%)		0/80 (0%)
Other (Not Including Serious) Adverse Events
	Nepafenac 0.3% Opthalmic Suspension		Ilevro 0.3% Opthalmic Suspension		Placebo (Vehicle) Opthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/175 (30.9%)		42/174 (24.1%)		26/80 (32.5%)
Ear and labyrinth disorders
Vertigo	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Eye disorders
Altered visual depth perception	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Anterior chamber cell	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Anterior chamber disorder	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Anterior chamber fibrin	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Anterior chamber inflammation	4/175 (2.3%)		2/174 (1.1%)		2/80 (2.5%)
Blepharitis	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Chalazion	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Conjunctival cyst	2/175 (1.1%)		0/174 (0%)		0/80 (0%)
Conjunctival haemorrhage	1/175 (0.6%)		2/174 (1.1%)		0/80 (0%)
Conjunctival hyperaemia	1/175 (0.6%)		2/174 (1.1%)		1/80 (1.3%)
Conjunctivitis allergic	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Corneal disorder	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Corneal oedema	2/175 (1.1%)		2/174 (1.1%)		4/80 (5%)
Eye discharge	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Eye inflammation	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Eye irritation	0/175 (0%)		0/174 (0%)		2/80 (2.5%)
Eye pain	4/175 (2.3%)		3/174 (1.7%)		4/80 (5%)
Eye pruritus	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Eyelid exfoliation	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Foreign body sensation in eyes	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Hypotony of eye	0/175 (0%)		1/174 (0.6%)		1/80 (1.3%)
Keratic precipitates	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Macular oedema	2/175 (1.1%)		1/174 (0.6%)		0/80 (0%)
Ocular discomfort	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Ocular hyperaemia	0/175 (0%)		0/174 (0%)		3/80 (3.8%)
Ocular hypertention	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Ocular hypertension	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Open angle glaucoma	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Photophobia	1/175 (0.6%)		1/174 (0.6%)		3/80 (3.8%)
Photopsia	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Posterior capsule opacification	4/175 (2.3%)		1/174 (0.6%)		2/80 (2.5%)
Posterior capsule rupture	0/175 (0%)		3/174 (1.7%)		1/80 (1.3%)
Punctate keratitis	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Vision blurred	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Vitreous degeneration	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Vitreous detachment	2/175 (1.1%)		0/174 (0%)		0/80 (0%)
Vitreous floaters	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Dyspepsia	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Toothache	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Vomiting	2/175 (1.1%)		0/174 (0%)		0/80 (0%)
General disorders
Fatigue	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Inflammation	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Oedema peripheral	1/175 (0.6%)		1/174 (0.6%)		0/80 (0%)
Sensation of foreign body	1/175 (0.6%)		2/174 (1.1%)		1/80 (1.3%)
Immune system disorders
Allergy to arthropod bite	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Drug hypersensitivity	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Hypersensitivity	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Infections and infestations
Bronchitis	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Sinusitis	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Urinary tract infection	4/175 (2.3%)		1/174 (0.6%)		0/80 (0%)
Injury, poisoning and procedural complications
Corneal abrasion	1/175 (0.6%)		1/174 (0.6%)		0/80 (0%)
Exposure to toxic agent	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Fibrin deposition on lens postoperative	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Hyphaema	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Iris injury	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Post procedural inflammation	2/175 (1.1%)		0/174 (0%)		2/80 (2.5%)
Procedural pain	1/175 (0.6%)		2/174 (1.1%)		1/80 (1.3%)
Investigations
Blood glucose increased	5/175 (2.9%)		6/174 (3.4%)		1/80 (1.3%)
Blood pressure increased	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Intraocular pressure increased	8/175 (4.6%)		3/174 (1.7%)		1/80 (1.3%)
Metabolism and nutrition disorders
Diabetes mellitus	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/175 (0%)		4/174 (2.3%)		0/80 (0%)
Pain in extremity	0/175 (0%)		1/174 (0.6%)		1/80 (1.3%)
Nervous system disorders
Dizziness	1/175 (0.6%)		1/174 (0.6%)		0/80 (0%)
Headache	8/175 (4.6%)		8/174 (4.6%)		8/80 (10%)
Migraine	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Sciatica	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Psychiatric disorders
Anxiety	0/175 (0%)		0/174 (0%)		1/80 (1.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/175 (0.6%)		0/174 (0%)		0/80 (0%)
Sinus pain	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Skin and subcutaneous tissue disorders
Skin exfoliation	0/175 (0%)		1/174 (0.6%)		0/80 (0%)
Vascular disorders
Flushing	0/175 (0%)		0/174 (0%)		1/80 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.