A 1-year Study in Adolescents to Assess the Long-term Safety of Almotriptan Malate When Treating Their Migraine Headaches

• Sponsor: Janssen-Ortho LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00257010
• Collaborator: Ortho-McNeil Neurologics, Inc. (Industry)
• Enrollment: 447
• Locations: 49
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety of almotriptan malate (a migraine headache medication) in the treatment of migraine headaches in adolescents for up to one year.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Almotriptan Malate	Phase 3

Detailed Description

Almotriptan malate, and several other treatments for migraine headaches, known as triptans, are approved for the treatment of migraine headaches in adults. To date, none of these have been approved by the Food and Drug Administration (FDA) for use in adolescents. This is an open-label, multi-center study that will enroll approximately 450 patients aged 12 - 17 years old with a history of one to 14 migraines per month for the 6 months prior to entering the study. The total study duration will be up to one year. There is a screening phase to determine if the patient is eligible for study entry, followed by an open-label treatment phase that can last up to one year. Almotriptan malate 12.5 mg tablets will be used to treat all migraine headaches during the study, as needed. The primary outcome of the study is an assessment of the long-term safety of almotriptan malate in adolescent migraine sufferers. The study hypothesis is that the almotriptan malate will be safe and well tolerated in the treatment of adolescent migraine headaches. Safety measurements will be performed at set time points during the study and will include laboratory tests, physical and neurological exams, electrocardiograms (ECGs) and the incidence of adverse events. A diary will be completed by the patient for each migraine headache for which they take almotriptan malate. Migraine pain information and almotriptan malate use will be recorded in the headache diary. An equal number of patients in the 12 - 14 year old range as the 15 - 17 year old range will be enrolled. Patients will take one 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain. The dose may be repeated once if the pain continues 2 hours after the first dose, but no more than 2 doses can be taken within a 24-hour period. Study medication will be taken for up to one year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 447 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-Term, Open-Label Safety Study of Oral Almotriptan Malate 12.5 mg in the Treatment of Migraine in Adolescents
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Almotriptan Malate Patients will take one 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain	Drug: Almotriptan Malate; Patients will take one 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain

Outcome Measures

Primary Outcome Measures

1. Number of Pain Free Headaches at 2 and 24 Hours Post-Dose [2 hours and 24 hours post-dose]

   Headache pain free is defined as a decrease in baseline pain intensity from severe, moderate or mild to no pain, without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 2 (or 24) hours of first dose of study medication. Sustained pain free is defined as pain free at 2 and 24 hours without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 24 hours.

Secondary Outcome Measures

1. Number of Headaches Achieving Pain Relief at 2 and 24 Hours Post-Dose [2 hours and 24 hours post-dose]

   Headache pain relief is defined as a decrease in baseline pain intensity from either severe or moderate intensity to mild or no pain, without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 2 (or 24) hours of first dose of study medication. Sustained pain relief is defined as pain relief at 2 and 24 hours without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 24 hours.

2. Number of Headaches With Photophobia [Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose]

   Occurrence and intensity of photophobia post-dose of study medication. Photophobia is an abnormal sensitivity to or intolerance of light, especially by the eyes.

3. Number of Headaches With Phonophobia [Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose]

   Occurrence and intensity of phonophobia post-dose of study medication. Phonophobia is an abnormal sensitivity to or intolerance of noise.

4. Number of Headaches With Nausea [Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose]

   Occurrence and intensity of nausea post-dose of study medication. Nausea is a feeling of sickness characterized by gastrointestinal distress and an urge to vomit.

5. Number of Headaches With Vomiting [Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose]

   Occurrence and intensity of vomiting post-dose of study medication. Vomiting is an act or instance of disgorging the contents of the stomach through the mouth also called emesis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a history of migraine for at least one year

• Have an average of 1 - 14 migraines per month for the 6 months prior to study entry

• Able to swallow oral medication

• Able to complete a headache diary

• Only taking one migraine preventive medication and on the same dose of that medication for at least 30 days before entering the study)

Exclusion Criteria:

• Have an allergy to almotriptan malate or have stopped taking almotriptan malate due to side effects

• Have 15 or more days within a month in which you have a headache

• Usually experience migraine aura (most common symptoms being visual disturbances or tingling sensations before migraine pain begins) without a headache

• Experience more than 6 non-migraine headaches per month

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States
2		Montgomery	Alabama	United States
3		Oxford	Alabama	United States
4		Mesa	Arizona	United States
5		Phoenix	Arizona	United States
6		Jonesboro	Arkansas	United States
7		Little Rock	Arkansas	United States
8		Santa Monica	California	United States
9		Centennial	Colorado	United States
10		Denver	Colorado	United States
11		Loxahatchee	Florida	United States
12		Miami	Florida	United States
13		Orlando	Florida	United States
14		Tampa	Florida	United States
15		West Palm Beach	Florida	United States
16		Atlanta	Georgia	United States
17		Snellville	Georgia	United States
18		Idaho Falls	Idaho	United States
19		Chicago	Illinois	United States
20		Des Moines	Iowa	United States
21		Topeka	Kansas	United States
22		Witchita	Kansas	United States
23		Louisville	Kentucky	United States
24		Ann Arbor	Michigan	United States
25		Columbia	Missouri	United States
26		Saint Louis	Missouri	United States
27		Springfield	Missouri	United States
28		Endwell	New York	United States
29		Mineola	New York	United States
30		Mount Vernon	New York	United States
31		Plainview	New York	United States
32		Raleigh	North Carolina	United States
33		Cincinnati	Ohio	United States
34		Columbus	Ohio	United States
35		Oklahoma City	Oklahoma	United States
36		Philadelphia	Pennsylvania	United States
37		Pittsburgh	Pennsylvania	United States
38		Alcoa	Tennessee	United States
39		Bristol	Tennessee	United States
40		Germantown	Tennessee	United States
41		Morristown	Tennessee	United States
42		Nashville	Tennessee	United States
43		Dallas	Texas	United States
44		Fort Worth	Texas	United States
45		Houston	Texas	United States
46		San Antonio	Texas	United States
47		San Marcos	Texas	United States
48		Salt Lake City	Utah	United States
49		Madison	Wisconsin	United States

Sponsors and Collaborators

• Janssen-Ortho LLC
• Ortho-McNeil Neurologics, Inc.

Investigators

• Study Director: Janssen Ortho LLC Clinical Trial, Janssen-Ortho LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Long-Term, Open-Label Safety Study of Oral Almotriptan Malate 12.5 mg in the Treatment ofMigraine in Adolescents

Publications

None provided.

• Responsible Party: Janssen-Ortho LLC
• ClinicalTrials.gov Identifier: NCT00257010
• Other Study ID Numbers: CR002827; CAPSS-368
• First Posted: Nov 22, 2005
• Last Update Posted: Feb 21, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Janssen-Ortho LLC: Migraine; Almotriptan Malate; Headache; Triptan
• Additional relevant MeSH terms: Migraine Disorders; Almotriptan

Study Results

Participant Flow

Recruitment Details	This study was conducted at 55 sites in the United States.
Pre-assignment Detail	Of the 447 participants enrolled, 420 participants took at least one dose of study drug according to the Headache Record and were included in the analysis.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Period Title: Overall Study
STARTED	447
COMPLETED	319
NOT COMPLETED	128

Baseline Characteristics

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Overall Participants	447
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.4 (1.63)
Sex: Female, Male (Count of Participants)
Female	245 54.8%
Male	202 45.2%

Outcome Measures

1. Primary Outcome

Title	Number of Pain Free Headaches at 2 and 24 Hours Post-Dose
Description	Headache pain free is defined as a decrease in baseline pain intensity from severe, moderate or mild to no pain, without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 2 (or 24) hours of first dose of study medication. Sustained pain free is defined as pain free at 2 and 24 hours without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 24 hours.
Time Frame	2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	7941
Headaches Pain Free at 2 hours	3218
Headaches Pain Free at 24 hours	5236
Headaches Sustained Pain Free at 24 hours	3048

2. Secondary Outcome

Title	Number of Headaches Achieving Pain Relief at 2 and 24 Hours Post-Dose
Description	Headache pain relief is defined as a decrease in baseline pain intensity from either severe or moderate intensity to mild or no pain, without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 2 (or 24) hours of first dose of study medication. Sustained pain relief is defined as pain relief at 2 and 24 hours without the use of supplemental pain medication and/or anti-emetic medication (including a second dose of study medication) within 24 hours.
Time Frame	2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	6099
Headaches Pain Relief at 2 hours	3765
Headaches Pain Relief at 24 hours	4182
Headaches Sustained Pain Relief at 24 hours	3384

3. Secondary Outcome

Title	Number of Headaches With Photophobia
Description	Occurrence and intensity of photophobia post-dose of study medication. Photophobia is an abnormal sensitivity to or intolerance of light, especially by the eyes.
Time Frame	Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	8052
At baseline	6164
At 2 hours	3150
At 24 hours	936

4. Secondary Outcome

Title	Number of Headaches With Phonophobia
Description	Occurrence and intensity of phonophobia post-dose of study medication. Phonophobia is an abnormal sensitivity to or intolerance of noise.
Time Frame	Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	8052
At baseline	5783
At 2 hours	2847
At 24 hours	805

5. Secondary Outcome

Title	Number of Headaches With Nausea
Description	Occurrence and intensity of nausea post-dose of study medication. Nausea is a feeling of sickness characterized by gastrointestinal distress and an urge to vomit.
Time Frame	Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	8052
At baseline	3262
At 2 hours	1785
At 24 hours	542

6. Secondary Outcome

Title	Number of Headaches With Vomiting
Description	Occurrence and intensity of vomiting post-dose of study medication. Vomiting is an act or instance of disgorging the contents of the stomach through the mouth also called emesis.
Time Frame	Baseline (after onset of migraine headache pain and before treatment), 2 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population is defined as all enrolled participants who took at least one dose of study medication and for whom at least one post-dose efficacy assessment was available.

Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
Measure Participants	420
Measure headaches	8052
At baseline	357
At 2 hours	258
At 24 hours	107

Adverse Events

Time Frame	12 months
Arm/Group Title	Almotriptan Malate
Arm/Group Description	Participants received 12.5 mg almotriptan malate tablet by mouth after the onset of migraine headache pain.
All Cause Mortality
	Almotriptan Malate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Almotriptan Malate
	Affected / at Risk (%)	# Events
Total	8/420 (1.9%)
Cardiac disorders
Bradycardia Foetal	1/420 (0.2%)
Gastrointestinal disorders
Intussusception	1/420 (0.2%)
Infections and infestations
Appendicitis	2/420 (0.5%)
Gastroenteritis	1/420 (0.2%)
Injury, poisoning and procedural complications
Gun Shot Wound	1/420 (0.2%)
Post Procedural Haemorrhage	1/420 (0.2%)
Psychiatric disorders
Major Depression	1/420 (0.2%)
Other (Not Including Serious) Adverse Events
	Almotriptan Malate
	Affected / at Risk (%)	# Events
Total	282/420 (67.1%)
Blood and lymphatic system disorders
Anaemia	3/420 (0.7%)
Leukopenia	2/420 (0.5%)
Lymphadenopathy	2/420 (0.5%)
Cardiac disorders
Tachycardia	1/420 (0.2%)
Ventricular Hypertrophy	1/420 (0.2%)
Ear and labyrinth disorders
Cerumen Impaction	1/420 (0.2%)
Ear Pain	2/420 (0.5%)
Motion Sickness	1/420 (0.2%)
Eye disorders
Eye Allergy	1/420 (0.2%)
Eye Irritation	1/420 (0.2%)
Hypermetropia	1/420 (0.2%)
Myopia	1/420 (0.2%)
Scotoma	1/420 (0.2%)
Vision Blurred	1/420 (0.2%)
Gastrointestinal disorders
Abdominal Pain	2/420 (0.5%)
Abdominal Pain Upper	10/420 (2.4%)
Aphthous Stomatitis	1/420 (0.2%)
Chapped Lips	1/420 (0.2%)
Constipation	1/420 (0.2%)
Diarrhoea	8/420 (1.9%)
Dry Mouth	1/420 (0.2%)
Dyspepsia	3/420 (0.7%)
Flatulence	1/420 (0.2%)
Food Poisoning	2/420 (0.5%)
Gastritis	3/420 (0.7%)
Gastrooesophageal Reflux Disease	5/420 (1.2%)
Gingival Swelling	1/420 (0.2%)
Hypoaesthesia Oral	1/420 (0.2%)
Nausea	25/420 (6%)
Salivary Gland Disorder	1/420 (0.2%)
Stomach Discomfort	4/420 (1%)
Stomatitis	1/420 (0.2%)
Tooth Disorder	1/420 (0.2%)
Tooth Impacted	1/420 (0.2%)
Toothache	5/420 (1.2%)
Vomiting	23/420 (5.5%)
General disorders
Chills	2/420 (0.5%)
Fatigue	3/420 (0.7%)
Influenza Like Illness	2/420 (0.5%)
Malaise	1/420 (0.2%)
Non-Cardiac Chest Pain	1/420 (0.2%)
Oedema Peripheral	1/420 (0.2%)
Pain	5/420 (1.2%)
Pyrexia	15/420 (3.6%)
Vessel Puncture Site Bruise	1/420 (0.2%)
Hepatobiliary disorders
Biliary Colic	1/420 (0.2%)
Biliary Dyskinesia	1/420 (0.2%)
Cholecystitis	1/420 (0.2%)
Immune system disorders
Drug Hypersensitivity	1/420 (0.2%)
Hypersensitivity	6/420 (1.4%)
Seasonal Allergy	1/420 (0.2%)
Infections and infestations
Abscess Limb	1/420 (0.2%)
Acute Sinusitis	2/420 (0.5%)
Acute Tonsillitis	1/420 (0.2%)
Bacterial Infection	1/420 (0.2%)
Bronchitis	9/420 (2.1%)
Bronchitis Acute	1/420 (0.2%)
Candidiasis	1/420 (0.2%)
Cellulitis	1/420 (0.2%)
Coccidioidomycosis	1/420 (0.2%)
Conjunctivitis Infective	2/420 (0.5%)
Ear Infection	8/420 (1.9%)
Eye Infection	2/420 (0.5%)
Gastritis Viral	1/420 (0.2%)
Gastroenteritis	2/420 (0.5%)
Gastroenteritis Viral	15/420 (3.6%)
Gonorrhoea	1/420 (0.2%)
Gynaecological Chlamydia Infection	1/420 (0.2%)
Herpes Simplex	2/420 (0.5%)
Herpes Zoster	1/420 (0.2%)
Hordeolum	2/420 (0.5%)
Infectious Mononucleosis	3/420 (0.7%)
Influenza	14/420 (3.3%)
Localised Infection	1/420 (0.2%)
Mastitis	1/420 (0.2%)
Nail Infection	2/420 (0.5%)
Nasopharyngitis	52/420 (12.4%)
Otitis Externa	4/420 (1%)
Otitis Media	5/420 (1.2%)
Pelvic Inflammatory Disease	1/420 (0.2%)
Pertussis	1/420 (0.2%)
Pharyngitis	11/420 (2.6%)
Pharyngitis Streptococcal	18/420 (4.3%)
Pneumonia	1/420 (0.2%)
Pyelonephritis	1/420 (0.2%)
Respiratory Tract Infection	2/420 (0.5%)
Rhinitis	4/420 (1%)
Sinusitis	29/420 (6.9%)
Skin Infection	1/420 (0.2%)
Staphylococcal Infection	1/420 (0.2%)
Subcutaneous Abscess	1/420 (0.2%)
Tinea Infection	1/420 (0.2%)
Tonsillitis	3/420 (0.7%)
Upper Respiratory Tract Infection	28/420 (6.7%)
Urinary Tract Infection	5/420 (1.2%)
Vaginal Candidiasis	1/420 (0.2%)
Varicella	2/420 (0.5%)
Viraemia	1/420 (0.2%)
Viral Infection	13/420 (3.1%)
Viral Rhinitis	1/420 (0.2%)
Viral Upper Respiratory Tract Infection	8/420 (1.9%)
Vulvovaginal Mycotic Infection	1/420 (0.2%)
Vulvovaginitis Trichomonal	1/420 (0.2%)
Injury, poisoning and procedural complications
Animal Bite	1/420 (0.2%)
Chemical Eye Injury	1/420 (0.2%)
Clavicle Fracture	1/420 (0.2%)
Concussion	7/420 (1.7%)
Contusion	6/420 (1.4%)
Epicondylitis	1/420 (0.2%)
Excoriation	2/420 (0.5%)
Facial Bones Fracture	1/420 (0.2%)
Fall	1/420 (0.2%)
Foot Fracture	1/420 (0.2%)
Forearm Fracture	1/420 (0.2%)
Foreign Body Trauma	1/420 (0.2%)
Gun Shot Wound	1/420 (0.2%)
Hand Fracture	3/420 (0.7%)
Head Injury	1/420 (0.2%)
Injury	1/420 (0.2%)
Joint Injury	2/420 (0.5%)
Joint Sprain	12/420 (2.9%)
Ligament Injury	3/420 (0.7%)
Ligament Sprain	1/420 (0.2%)
Limb Injury	4/420 (1%)
Medical Device Pain	2/420 (0.5%)
Muscle Strain	2/420 (0.5%)
Periorbital Haematoma	1/420 (0.2%)
Post-Traumatic Pain	2/420 (0.5%)
Procedural Pain	3/420 (0.7%)
Skin Laceration	1/420 (0.2%)
Thermal Burn	1/420 (0.2%)
Tibia Fracture	1/420 (0.2%)
Upper Limb Fracture	1/420 (0.2%)
Wrist Fracture	3/420 (0.7%)
Investigations
Alanine Aminotransferase Increased	1/420 (0.2%)
Aspartate Aminotransferase Increased	1/420 (0.2%)
Blood Glucose Increased	2/420 (0.5%)
Blood Triglycerides Increased	1/420 (0.2%)
Blood Urine Present	1/420 (0.2%)
Electrocardiogram Pr Prolongation	1/420 (0.2%)
Electrocardiogram QRS Complex Prolonged	1/420 (0.2%)
Epstein-Barr Virus Test Positive	1/420 (0.2%)
Glucose Urine Present	1/420 (0.2%)
Haematocrit Decreased	1/420 (0.2%)
Haemoglobin Decreased	1/420 (0.2%)
Lymph Nodes Scan Abnormal	1/420 (0.2%)
Neutrophil Count Increased	1/420 (0.2%)
Protein Urine	2/420 (0.5%)
Protein Urine Present	2/420 (0.5%)
Red Blood Cell Count Decreased	1/420 (0.2%)
Red Blood Cells Urine	1/420 (0.2%)
Spleen Palpable	1/420 (0.2%)
Weight Decreased	2/420 (0.5%)
Weight Increased	2/420 (0.5%)
White Blood Cell Count Increased	1/420 (0.2%)
White Blood Cells Urine Positive	1/420 (0.2%)
Metabolism and nutrition disorders
Dehydration	2/420 (0.5%)
Increased Appetite	1/420 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/420 (1.4%)
Back Pain	6/420 (1.4%)
Muscle Spasms	5/420 (1.2%)
Muscle Tightness	3/420 (0.7%)
Muscular Weakness	1/420 (0.2%)
Musculoskeletal Chest Pain	1/420 (0.2%)
Myalgia	2/420 (0.5%)
Neck Pain	2/420 (0.5%)
Pain in Extremity	4/420 (1%)
Scoliosis	1/420 (0.2%)
Temporomandibular Joint Syndrome	2/420 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	1/420 (0.2%)
Neuroma	1/420 (0.2%)
Nervous system disorders
Disturbance in Attention	1/420 (0.2%)
Dizziness	8/420 (1.9%)
Facial Neuralgia	1/420 (0.2%)
Headache	8/420 (1.9%)
Hyperreflexia	2/420 (0.5%)
Hypoaesthesia	2/420 (0.5%)
Loss of Consciousness	1/420 (0.2%)
Migraine	6/420 (1.4%)
Paraesthesia	2/420 (0.5%)
Paraesthesia Oral	1/420 (0.2%)
Post-Traumatic Headache	2/420 (0.5%)
Psychomotor Hyperactivity	1/420 (0.2%)
Somnolence	6/420 (1.4%)
Syncope	5/420 (1.2%)
Tension Headache	1/420 (0.2%)
Psychiatric disorders
Affective Disorder	1/420 (0.2%)
Agitation	1/420 (0.2%)
Anxiety	1/420 (0.2%)
Attention Deficit/Hyperactivity Disorder	4/420 (1%)
Depression	1/420 (0.2%)
Insomnia	8/420 (1.9%)
Mood Altered	1/420 (0.2%)
Sleep Disorder	1/420 (0.2%)
Stress	1/420 (0.2%)
Renal and urinary disorders
Dysuria	1/420 (0.2%)
Enuresis	1/420 (0.2%)
Urinary Retention	1/420 (0.2%)
Reproductive system and breast disorders
Dysmenorrhoea	7/420 (1.7%)
Menstruation Irregular	2/420 (0.5%)
Oligomenorrhoea	1/420 (0.2%)
Ovarian Cyst Ruptured	1/420 (0.2%)
Respiratory, thoracic and mediastinal disorders
Allergic Cough	1/420 (0.2%)
Allergic Respiratory Symptom	1/420 (0.2%)
Asthma	2/420 (0.5%)
Asthma Exercise Induced	3/420 (0.7%)
Bronchial Hyperactivity	1/420 (0.2%)
Cough	16/420 (3.8%)
Dyspnoea	1/420 (0.2%)
Epistaxis	3/420 (0.7%)
Hyperventilation	1/420 (0.2%)
Nasal Congestion	17/420 (4%)
Pharyngolaryngeal Pain	27/420 (6.4%)
Productive Cough	1/420 (0.2%)
Rhinitis Allergic	2/420 (0.5%)
Rhinorrhoea	7/420 (1.7%)
Sinus Congestion	4/420 (1%)
Sneezing	2/420 (0.5%)
Throat Irritation	1/420 (0.2%)
Upper Respiratory Tract Congestion	5/420 (1.2%)
Skin and subcutaneous tissue disorders
Acne	4/420 (1%)
Dermatitis	1/420 (0.2%)
Dermatitis Atopic	1/420 (0.2%)
Dermatitis Contact	6/420 (1.4%)
Drug Eruption	1/420 (0.2%)
Eczema	2/420 (0.5%)
Hirsutism	1/420 (0.2%)
Pain of Skin	2/420 (0.5%)
Petechiae	2/420 (0.5%)
Pigmentation Disorder	1/420 (0.2%)
Precancerous Skin Lesion	1/420 (0.2%)
Rash	5/420 (1.2%)
Rash Generalised	1/420 (0.2%)
Rash Pruritic	1/420 (0.2%)
Scar	1/420 (0.2%)
Skin Striae	1/420 (0.2%)
Urticaria	1/420 (0.2%)
Vitiligo	1/420 (0.2%)
Surgical and medical procedures
Tooth Extraction	1/420 (0.2%)
Vascular disorders
Hot Flush	1/420 (0.2%)
Systolic Hypertension	1/420 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.