Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers

• Sponsor: Egalet Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01355588
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 4
• Duration (Months): 7
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This was a phase 1, double-blind, 4-way crossover study in healthy male and female volunteers. Subjects received 4 formulations of intranasal ketorolac tromethamine 30 mg. There was a wash-out period of 3-7 days between each dose. On Day 1 of each period subjects were randomised to receive either a single intranasal dose of 30 mg ketorolac tromethamine alone or single intranasal dose of 30 mg ketorolac tromethamine with 4%, 5% or 6% lidocaine hydrochloride. At the end of the study each subject had received all 4 treatments.

The primary objective of this study in healthy volunteers was to compare the safety, tolerability, and pharmacokinetics of 4 formulations of ketorolac tromethamine. A secondary objective was to monitor lidocaine hydrochloride plasma levels.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Ketorolac Tromethamine; Drug: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl); Drug: Ketorolac Tromethamine with 5% Lidocaine HCl; Drug: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Double-blind, 4-way Crossover Study of the Tolerability, Safety and Pharmacokinetics of 4 Formulations of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Sep 1, 2005
• Actual Study Completion Date: Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketorolac Tromethamine	Drug: Ketorolac Tromethamine; 30 mg Ketorolac Tromethamine intranasal (IN)
Experimental: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)	Drug: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl); 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN
Experimental: Ketorolac Tromethamine with 5% Lidocaine HCl	Drug: Ketorolac Tromethamine with 5% Lidocaine HCl; 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Experimental: Ketorolac Tromethamine with 6% Lidocaine HCl	Drug: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl; 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose]

2. Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t) [Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose]

3. Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞) [Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose]

Secondary Outcome Measures

1. Time to Reach Maximum Plasma Concentration (Tmax) [Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female volunteers, aged 18 to 60 years inclusive

• Female subjects of child bearing potential must have had a negative urine pregnancy test prior to entry into the study and must not have been breast feeding

• All female subjects of child bearing potential and all male subjects with female partners of child bearing potential must have consented to use a medically acceptable method of contraception (oral or implanted contraceptive hormones, condom or diaphragm with spermicidal agent, intrauterine device or surgical sterilisation) throughout the study period

• Subject had given signed informed consent

• Subject was within 20% of normal weight for his/her height and body build according to the table of "Desirable Weights for Men and Women" (Metropolitan Life Insurance Co.

• Subject's medical history was considered normal, with no clinically significant abnormalities

• Subject was considered to be in good health in the opinion of the Investigator as determined by a pre-study physical examination with no clinically significant abnormalities, vital signs within normal range and an ECG with no clinically significant abnormalities

• Subject's pre-study clinical laboratory findings were within normal range or, if outside of the normal range, not deemed clinically significant in the opinion of the Investigator

• Subject had bilateral patent nasal airways at screening as assessed by the Investigator

• Body weight was at least 70 kg

Exclusion Criteria:

• Subject had a clinically significant illness in the 4 weeks before screening

• Use of prescribed medications in the 3 weeks prior to dosing or over-the-counter preparations for 7 days prior to dosing, except paracetamol which was allowed up to 48 hours prior to dosing. However, use of multivitamins and oral contraceptives were permitted

• Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening

• Subject had history of alcohol abuse or drank in excess of 28 units per week (males) or 21 units per week (females)

• Current tobacco use or a history of smoking within the past 5 years

• Subject was, in the opinion of the Investigator, not suitable to participate in the study

• Subjects who had participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing

• Subjects who had a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen

• Subjects with a serious adverse reaction or significant hypersensitivity to any drug

• Subjects who has donated 500 mL or more of blood within the 3 months prior to screening

• Any history of co-existing nasal polyps, NSAID sensitivity and asthma

• Allergic reaction to aspirin or other NSAIDs

• Current upper respiratory tract infection or other respiratory tract condition that could have interfered with the absorption of the nasal spray or with the assessment of AEs

• Any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)

• Use of a monoamine oxidase inhibitor in the 14 days prior to study entry

• Active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding

• Anemia due to unexplained or known gastrointestinal bleeding

• History of asthma or any other chronic pulmonary disorder

• Renal impairment or a risk of renal failure due to volume depletion

• Known sensitivity to lidocaine hydrochloride

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medeval Ltd	Manchester		United Kingdom

Sponsors and Collaborators

• Egalet Ltd

Investigators

• Principal Investigator: Cyril Clarke, BSc MB BS MFPM, Medeval Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Egalet Ltd
• ClinicalTrials.gov Identifier: NCT01355588
• Other Study ID Numbers: ROX 2005-02
• First Posted: May 18, 2011
• Last Update Posted: Mar 16, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Ketorolac; Ketorolac Tromethamine; Lidocaine

Study Results

Participant Flow

Recruitment Details	1 month and 2 weeks; Medeval Limited Skelton House, Manchester Science Park, Lloyd Street North, Manchester M15 6SH, U.K.

Arm/Group Title	Treatment A, Treatment C, Treatment D, Treatment B	Treatment B, Treatment D, Treatment C, Treatment A	Treatment C, Treatment B, Treatment A, Treatment D	Treatment D, Treatment A, Treatment B, Treatment C
Arm/Group Description	Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN	Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Day 1)
STARTED	4	4	4	4
COMPLETED	4	4	4	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Treatment A, Treatment C, Treatment D, Treatment B	Treatment B, Treatment D, Treatment C, Treatment A	Treatment C, Treatment B, Treatment A, Treatment D	Treatment D, Treatment A, Treatment B, Treatment C	Total
Arm/Group Description	Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN, then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN	Treatment D: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN, then; Treatment A: Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN), then; Treatment B: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN, then; Treatment C: Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN	Total of all reporting groups
Overall Participants	4	4	4	4	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	4 100%	4 100%	4 100%	16 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.25 (17.21)	40.75 (19.97)	34.0 (15.90)	50.25 (10.31)	39.8 (16.0)
Sex: Female, Male (Count of Participants)
Female	2 50%	0 0%	1 25%	2 50%	5 31.3%
Male	2 50%	4 100%	3 75%	2 50%	11 68.8%
Region of Enrollment (participants) [Number]
United Kingdom	4 100%	4 100%	4 100%	4 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine	Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)	Ketorolac Tromethamine With 5% Lidocaine HCl	Ketorolac Tromethamine With 6% Lidocaine HCl
Arm/Group Description	Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN	30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Measure Participants	16	16	16	16
Mean (Standard Deviation) [ng/mL]	2059.6 (801.7)	1963.1 (1020.8)	1799.9 (714.1)	2048.5 (817.6)

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t)
Time Frame	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine	Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)	Ketorolac Tromethamine With 5% Lidocaine HCl	Ketorolac Tromethamine With 6% Lidocaine HCl
Arm/Group Description	Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN	30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Measure Participants	16	16	16	16
Mean (Standard Deviation) [ng*h/mL]	8440.6 (4021.2)	7856.0 (4211.8)	7561.5 (4051.2)	8103.8 (3786.3)

3. Primary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞)
Time Frame	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine	Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)	Ketorolac Tromethamine With 5% Lidocaine HCl	Ketorolac Tromethamine With 6% Lidocaine HCl
Arm/Group Description	Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN	30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Measure Participants	16	16	16	16
Mean (Standard Deviation) [ng*h/mL]	9061.9 (4526.8)	8694.5 (4477.1)	8086.8 (4608.2)	8677.6 (4301.0)

4. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax)
Time Frame	Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketorolac Tromethamine	Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)	Ketorolac Tromethamine With 5% Lidocaine HCl	Ketorolac Tromethamine With 6% Lidocaine HCl
Arm/Group Description	Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)	Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN	Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN	30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
Measure Participants	16	16	16	16
Median (Full Range) [hours]	0.510	0.500	0.390	0.410

Adverse Events

Time Frame	1 month and 2 weeks
Arm/Group Title	Ketorolac Tromethamine		Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)		Ketorolac Tromethamine With 5% Lidocaine HCl		Ketorolac Tromethamine With 6% Lidocaine HCl
Arm/Group Description	Ketorolac Tromethamine : 30 mg Ketorolac Tromethamine intranasal (IN)		Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) : 30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN		Ketorolac Tromethamine with 5% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN		30 mg Ketorolac Tromethamine with 6% Lidocaine HCl : 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN
All Cause Mortality
	Ketorolac Tromethamine		Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)		Ketorolac Tromethamine With 5% Lidocaine HCl		Ketorolac Tromethamine With 6% Lidocaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketorolac Tromethamine		Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)		Ketorolac Tromethamine With 5% Lidocaine HCl		Ketorolac Tromethamine With 6% Lidocaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Ketorolac Tromethamine		Ketorolac Tromethamine With 4% Lidocaine Hydrochloride (HCl)		Ketorolac Tromethamine With 5% Lidocaine HCl		Ketorolac Tromethamine With 6% Lidocaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/16 (68.8%)		9/16 (56.3%)		9/16 (56.3%)		8/16 (50%)
General disorders
Fatigue	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Infections and infestations
Nasopharyngitis	1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)
Rhinitis	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Nervous system disorders
Headache	1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Psychiatric disorders
Nervousness	1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Reproductive system and breast disorders
Dysmenorrhea	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/16 (12.5%)		1/16 (6.3%)		1/16 (6.3%)		1/16 (6.3%)
Nasal discomfort	6/16 (37.5%)		6/16 (37.5%)		6/16 (37.5%)		6/16 (37.5%)
Nasal oedema	9/16 (56.3%)		3/16 (18.8%)		6/16 (37.5%)		3/16 (18.8%)
Nasal septum ulceration	1/16 (6.3%)		2/16 (12.5%)		0/16 (0%)		0/16 (0%)
Pharyngolaryngeal pain	0/16 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)
Rhinorrhea	1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)
Vascular disorders
Hematoma	0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)
Hot flush	0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (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.