NGF-Glaucoma: Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma

• Sponsor: Dompé Farmaceutici S.p.A (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02855450
• Collaborator: Cromsource (Industry)
• Enrollment: 60
• Location: 1
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the safety and tolerability of a 180μg/ml TID dose regimen of recombinant human nerve growth factor (rhNGF) eye drop solution administered over 8 weeks versus a vehicle control in patients with progressive primary open-angle glaucoma despite IOP control.

The secondary objectives are to measure the changes in BCDVA, visual field, ERG and structural changes in ganglion cell layer and nerve fiber layer thickness measured by optical coherence tomography. The secondary outcomes will be examined at 1, 4 and 8 weeks of therapy, and at 4 and 24 weeks after cessation of therapy (Week 12 visit and Week 32 visit), and will include functional assessments to investigate evidence of a persistent biological effect after discontinuation of the study treatment.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: rhNGF; Drug: Vehicle	Phase 1

Detailed Description

This is an 8 Week phase Ib, monocentric, randomized, double-masked, vehicle controlled, parallel groups, study with a 24 Week follow-up period to evaluate the safety and potential efficacy of a 180 μg/ml recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in 60 study participants with chronic primary open angle glaucoma.

Participants may qualify with either progressive optic neuropathy despite maximal current therapy (i.e. IOP reduction), or with stabilized IOP but diminished vision (central or peripheral).

Participants with a qualifying eye will be randomized 2:1 to topical recombinant human nerve growth factor (rhNGF) therapy or vehicle placebo control. Examinations for safety and efficacy will occur one week following initiation of therapy, and at 4, 8, 12 and 32 weeks.

All participants in either arm will be followed clinically at 4 weeks after cessation of therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An 8 Week Phase Ib, Monocentric, Randomized, Double-masked, Parallel Groups, Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of a 180 μg/ml rhNGF Eye Drops Solution Vs Vehicle in Patients With Glaucoma
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: May 1, 2018
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rhNGF rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution	Drug: rhNGF; Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.; Other Names: cenegermin
Placebo Comparator: Vehicle Ophthalmic Placebo solution	Drug: Vehicle; Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Incidence of Events as of Primary Safety Outcomes [At day 56/end of treatment]

   Unexpected Severe Progression Of Optic Neuropathy (USPON) is a composed parameter which required at least 28 single evaluations; it occurred if the subject answered Yes to any of the following 4 questions on unexpected severe progression: Best Corrected Distance Visual Acuity (BCDVA): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Humphrey Visual Field (HVF): 'Yes' for at least one treated eye in at least one assessment during treatment or follow-up period Electroretinography (ERG): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Optical Coherence tomography (OCT): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Intolerance and allergy to the drug was identified based on preferred term of treatment-emergent adverse events. URAEs are unexpected related AE affecting ocular function. Local/systemic toxicities were identified via the AE form

2. Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score [Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)]

   A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale. Only "overall" values for primary eye and secondary eye are reported here under. An eye was considered as Primary eye, if the eye was treated and the investigator considered this eye as qualifying eye. If both eyes were considered as qualifying eye, the right eye was chosen. The other eye was then considered as Secondary eye, if the eye was treated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients 18 years of age or older. Participant must understand and sign the informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety.

2. Participant's clinical diagnosis must be consistent with glaucoma characterized by the following features: a) clinical evidence of progressive RGC dysfunction and degeneration using visual field and/or a structural modality. There must be at least 3 reliable visual fields within 14 months prior to entering into the study; b) residual visual field preservation in at least 1 quadrant.

3. Participant must be medically able to undergo the testing required in the flowsheet of exam procedures.

4. Females of childbearing potential must agree to use an effective form of birth control.

Exclusion Criteria:

1. Participant has another optic nerve or retinal degenerative disease or co-morbidity causing significant vision loss, irrespective of whether it is currently treated or untreated, that could limit the possibility of visual recovery.

2. Participant is blind in one eye.

3. Participant has a requirement of acyclovir and/or related products during study duration. 4- Participant has evidence of corneal opacification or lack of optical clarity.

4. Participant has evidence of corneal opacification or lack of optical clarity.

5. Participant has undergone lens removal in the last 3 months, with or without intra-ocular lens implantation, or has undergone intra-ocular lens replacement within 3 months, or has undergone any other ocular surgery within 9 months prior to initiation of study drug.

6. Participant is receiving systemic steroids or other immunosuppressive medications.

7. Participant is currently participating in or has within the last 3 months participated in any other clinical trial of a non-clinically approved drug by ocular or systemic administration.

8. Participant has uveitis or other ocular inflammatory disease.

9. Participant has diabetic macular edema.

10. Participant has a history of ocular herpes zoster.

11. Participant is on chemotherapy.

12. Participant has a history of malignancy, not counting basal cell carcinomas, UNLESS it was treated successfully 2 years prior to inclusion in the trial.

13. Known hypersensitivity to one of the components of the study or procedural medications.

14. History of drug, medication or alcohol abuse or addiction.

15. Females of childbearing potential (those who are not surgically sterilized or post- menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:

16. are currently pregnant or,

17. have a positive result on the urine pregnancy test at the Screening/Baseline Visit or,

18. intend to become pregnant during the study treatment period or,

19. are breast-feeding or,

20. not willing to use highly effective birth control measures, such as: Hormonal contraceptives - oral, implanted, transdermal, or injected and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or IUD during the entire course of and 30 days after the study treatment periods.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Byers Eye Institute at Stanford University	Palo Alto	California	United States	94303

Sponsors and Collaborators

• Dompé Farmaceutici S.p.A
• Cromsource

Investigators

• Principal Investigator: Jeffrey L Goldberg, MD, PhD, , MD, PhD

Study Documents (Full-Text)

• Study Protocol - Nov 4, 2016
• Statistical Analysis Plan - Feb 9, 2018

More Information

Publications

None provided.

• Responsible Party: Dompé Farmaceutici S.p.A
• ClinicalTrials.gov Identifier: NCT02855450
• Other Study ID Numbers: NGF0314
• First Posted: Aug 4, 2016
• Last Update Posted: Nov 25, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glaucoma

Study Results

Participant Flow

Arm/Group Title	rhNGF	Vehicle
Arm/Group Description	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Period Title: Overall Study
STARTED	40	20
COMPLETED	35	20
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	rhNGF	Vehicle	Total
Arm/Group Description	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.	Total of all reporting groups
Overall Participants	40	20	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 37.5%	12 60%	27 45%
>=65 years	25 62.5%	8 40%	33 55%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.0 (13.98)	62.2 (13.28)	66.1 (13.92)
Sex: Female, Male (Count of Participants)
Female	14 35%	9 45%	23 38.3%
Male	26 65%	11 55%	37 61.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5%	1 5%	3 5%
Not Hispanic or Latino	38 95%	19 95%	57 95%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	20 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Events as of Primary Safety Outcomes
Description	Unexpected Severe Progression Of Optic Neuropathy (USPON) is a composed parameter which required at least 28 single evaluations; it occurred if the subject answered Yes to any of the following 4 questions on unexpected severe progression: Best Corrected Distance Visual Acuity (BCDVA): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Humphrey Visual Field (HVF): 'Yes' for at least one treated eye in at least one assessment during treatment or follow-up period Electroretinography (ERG): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Optical Coherence tomography (OCT): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Intolerance and allergy to the drug was identified based on preferred term of treatment-emergent adverse events. URAEs are unexpected related AE affecting ocular function. Local/systemic toxicities were identified via the AE form
Time Frame	At day 56/end of treatment

Outcome Measure Data

Analysis Population Description

Safety Set (SAF). The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received

Arm/Group Title	rhNGF	Vehicle
Arm/Group Description	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Measure Participants	40	20
USPON	0	2
USPON during treatment period	0	0
Intolerance to the drug	6	0
Ocular URAEs	1	1
Local/systemic toxicities	0	0

2. Primary Outcome

Title	Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score
Description	A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale. Only "overall" values for primary eye and secondary eye are reported here under. An eye was considered as Primary eye, if the eye was treated and the investigator considered this eye as qualifying eye. If both eyes were considered as qualifying eye, the right eye was chosen. The other eye was then considered as Secondary eye, if the eye was treated.
Time Frame	Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)

Outcome Measure Data

Analysis Population Description

The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received. Please note that there were major protocol deviations, so that no complete VAS data was reported during treatment period; for this reason the numbers of participants analyzed per row may differ from the Overall Numbers of Participants.

Arm/Group Title	rhNGF	Vehicle
Arm/Group Description	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Measure Participants	40	20
Day 7 - primary eye	2.8 (9.09)	-2.1 (5.95)
Day 28 - primary eye	4.0 (11.22)	1.0 (11.85)
Day 56 - primary eye	3.6 (16.08)	-0.9 (6.51)
Day 84 - primary eye	-0.3 (11.81)	0.3 (6.78)
Day 7 - secondary eye	2.1 (9.44)	-1.4 (6.45)
Day 28 - secondary eye	4.6 (13.25)	1.2 (12.16)
Day 56 - secondary eye	4.5 (16.64)	0.6 (10.60)
Day 84 - secondary eye	-0.7 (12.95)	1.5 (10.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 7 and primary eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	ANCOVA
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95%; 0.2 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 28 and primary eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.457
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 95%; -4.1 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 56 and primary eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.283
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -3.5 to 11.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 7 and secondary eye
	Type of Statistical Test	Superiority
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
Statistical Test of Hypothesis	p-Value	0.147
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -1.3 to 8.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 28 and secondary eye
	Type of Statistical Test	Superiority
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -4.4 to 10.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	rhNGF, Vehicle
	Comments	These statistics refer to Day 56 and secondary eye
	Type of Statistical Test	Superiority
	Comments	Analysis results are obtained from an ANCOVA with treatment as factor and baseline value as covariate.
Statistical Test of Hypothesis	p-Value	0.327
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -4.4 to 13.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224
Adverse Event Reporting Description	A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Arm/Group Title	rhNGF		Vehicle
Arm/Group Description	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.		Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
All Cause Mortality
	rhNGF		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/20 (0%)
Serious Adverse Events
	rhNGF		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/40 (7.5%)		2/20 (10%)
Cardiac disorders
Angina unstable	0/40 (0%)	0	1/20 (5%)	1
Atrial fibrillation	1/40 (2.5%)	1	0/20 (0%)	0
Cardiac failure congestive	1/40 (2.5%)	1	0/20 (0%)	0
Infections and infestations
Mycobacterium avium complex infection	0/40 (0%)	0	1/20 (5%)	1
Injury, poisoning and procedural complications
Radius fracture	0/40 (0%)	0	1/20 (5%)	1
Metabolism and nutrition disorders
Hyperglycaemia	1/40 (2.5%)	1	0/20 (0%)	0
Hyponatraemia	1/40 (2.5%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis fungoides	1/40 (2.5%)	1	0/20 (0%)	0
Nervous system disorders
Cerebral infarction	1/40 (2.5%)	1	0/20 (0%)	0
Vascular disorders
Aortic stenosis	1/40 (2.5%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	rhNGF		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/40 (77.5%)		9/20 (45%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/40 (0%)	0	1/20 (5%)	1
Eye disorders
Eye pain	21/40 (52.5%)	26	2/20 (10%)	2
Eye irritation	6/40 (15%)	7	3/20 (15%)	3
Photophobia	8/40 (20%)	8	0/20 (0%)	0
Conjunctival hyperaemia	3/40 (7.5%)	4	1/20 (5%)	1
Blepharitis	3/40 (7.5%)	3	1/20 (5%)	1
Vision blurred	3/40 (7.5%)	3	1/20 (5%)	1
Dry eye	2/40 (5%)	2	1/20 (5%)	1
Foreign body sensation in eyes	2/40 (5%)	2	1/20 (5%)	1
Lacrimation increased	2/40 (5%)	2	1/20 (5%)	1
Uveitis	2/40 (5%)	2	0/20 (0%)	0
Abnormal sensation in eye	0/40 (0%)	0	1/20 (5%)	1
Blepharochalasis	1/40 (2.5%)	1	0/20 (0%)	0
Chalazion	1/40 (2.5%)	1	0/20 (0%)	0
Conjunctival oedema	1/40 (2.5%)	1	0/20 (0%)	0
Eye inflammation	1/40 (2.5%)	1	0/20 (0%)	0
Eye swelling	1/40 (2.5%)	1	0/20 (0%)	0
Eyelid oedema	1/40 (2.5%)	1	0/20 (0%)	0
Eyelid pain	1/40 (2.5%)	1	0/20 (0%)	0
Eyelid ptosis	1/40 (2.5%)	1	0/20 (0%)	0
Keratitis	1/40 (2.5%)	1	0/20 (0%)	0
Meibonian gland dysfunction	1/40 (2.5%)	1	0/20 (0%)	0
Ocular discomfort	1/40 (2.5%)	1	0/20 (0%)	0
Ocular hyperaemia	1/40 (2.5%)	1	0/20 (0%)	0
Punctate keratitis	0/40 (0%)	0	1/20 (5%)	1
Retinal haemorrhage	1/40 (2.5%)	1	0/20 (0%)	0
Vitreous haemorrhage	1/40 (2.5%)	1	0/20 (0%)	0
General disorders
Peripheral swelling	1/40 (2.5%)	1	0/20 (0%)	0
Infections and infestations
Bronchitis	1/40 (2.5%)	1	0/20 (0%)	0
Loer respiratory tract infection	0/40 (0%)	0	1/20 (5%)	1
Investigations
Intraocular pressure increased	2/40 (5%)	3	1/20 (5%)	1
Intraocular pressure test abnormal	1/40 (2.5%)	1	0/20 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/40 (2.5%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/40 (2.5%)	1	0/20 (0%)	0
Joint swelling	1/40 (2.5%)	1	0/20 (0%)	0
Pain in extremity	1/40 (2.5%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease	1/40 (2.5%)	1	0/20 (0%)	0
Squamous cell carcinoma	1/40 (2.5%)	1	0/20 (0%)	0
Nervous system disorders
Haedache	4/40 (10%)	4	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal discomfort	1/40 (2.5%)	1	0/20 (0%)	0
Oropharyngeal pain	1/40 (2.5%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/40 (2.5%)	1	0/20 (0%)	0
Surgical and medical procedures
Medical device implantation	0/40 (0%)	0	1/20 (5%)	2
Photocoagulation	1/40 (2.5%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.