Trial Outcomes & Findings for Long-Term Exposure to Rizatriptan 5-mg and 10-mg Oral Tablet (Combined Extension Protocols MK-0462-022, MK-0462-025, MK-0462-029) (NCT NCT01286207)

Last Updated: 2022-02-03

Results Overview

Headache severity was rated on a 4-point scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain) immediately before initial dose and at 2 hours thereafter. Pain relief was defined as a reduction of headache severity from grades 2/3 at baseline to 0/1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1959 participants

Primary outcome timeframe

2 hours after initial dose of test drug

Results posted on

2022-02-03

Participant Flow

All participants that completed protocol MK-0462-022 (NCT00897949), MK-0462-025 (NCT00899379), or MK-0462-029 (NCT00897104) and consented to continue in the studies up to 12 months were included in this pooled extension data.

Participant milestones

Participant milestones
Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care Standard care at onset of migraine attack
Overall Study STARTED	751	857	351
Overall Study COMPLETED	453	609	261
Overall Study NOT COMPLETED	298	248	90

Reasons for withdrawal

Reasons for withdrawal
Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care Standard care at onset of migraine attack
Overall Study Adverse Event	27	41	8
Overall Study Lost to Follow-up	49	43	20
Overall Study Withdrawal by Subject	93	79	41
Overall Study Lack of Response	92	38	8
Overall Study Other	37	47	13

Baseline Characteristics

Long-Term Exposure to Rizatriptan 5-mg and 10-mg Oral Tablet (Combined Extension Protocols MK-0462-022, MK-0462-025, MK-0462-029)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rizatriptan 5 mg n=751 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=857 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=351 Participants Standard care at onset of migraine attack	Total n=1959 Participants Total of all reporting groups
Age, Continuous	41.6 years n=5 Participants	41.1 years n=7 Participants	40.7 years n=5 Participants	41.2 years n=4 Participants
Sex: Female, Male Female	643 Participants n=5 Participants	727 Participants n=7 Participants	300 Participants n=5 Participants	1670 Participants n=4 Participants
Sex: Female, Male Male	108 Participants n=5 Participants	130 Participants n=7 Participants	51 Participants n=5 Participants	289 Participants n=4 Participants

PRIMARY outcome

Timeframe: 2 hours after initial dose of test drug

Population: All patients who took study medication and filled out their diary cards were included in the analysis of efficacy. No data were imputed.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=606 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=815 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=325 Participants Standard care at onset of migraine attack
Percent of Patient's Headaches With Pain Relief at 2 Hours After the Initial Dose of Test Drug	80 percent of headaches Interval 55.6 to 93.8	89.5 percent of headaches Interval 75.0 to 98.0	69.6 percent of headaches Interval 46.2 to 92.0

PRIMARY outcome

Timeframe: Up to 12 months

Population: All patients who took study medication were included in the analysis.

Serious clinical adverse experiences (CAEs) are any adverse events (AEs) occurring at any dose that; results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer; or is an overdose.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=711 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=834 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=334 Participants Standard care at onset of migraine attack
Number of Participants With Serious Clinical Adverse Experiences With Serious CAEs	13 participants	17 participants	10 participants
Number of Participants With Serious Clinical Adverse Experiences Without Serious CAEs	698 participants	817 participants	324 participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: All patients who took study medication were included in the analysis.

Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=711 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=834 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=334 Participants Standard care at onset of migraine attack
Number of Participants With Drug-related Clinical Adverse Experiences With drug-related CAEs	288 participants	456 participants	139 participants
Number of Participants With Drug-related Clinical Adverse Experiences Without drug-related CAEs	423 participants	378 participants	195 participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: All patients who took study medication were included in the analysis.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=711 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=834 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=334 Participants Standard care at onset of migraine attack
Number of Participants Who Discontinued Due to Clinical Adverse Experiences Discontinued due to CAEs	26 participants	37 participants	7 participants
Number of Participants Who Discontinued Due to Clinical Adverse Experiences Not discontinued due to CAEs	685 participants	797 participants	327 participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: All patients who took study medication and had lab test(s)were included in the analysis.

Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) laboratory adverse experience (LAE). A LAE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=709 Participants Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=827 Participants Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=333 Participants Standard care at onset of migraine attack
Number of Participants With Drug-related Lab Adverse Experiences	15 participants	23 participants	4 participants

Adverse Events

Rizatriptan 5 mg

Serious events: 13 serious events

Other events: 492 other events

Deaths: 0 deaths

Rizatriptan 10 mg

Serious events: 17 serious events

Other events: 679 other events

Deaths: 0 deaths

Standard Care

Serious events: 10 serious events

Other events: 267 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Rizatriptan 5 mg n=711 participants at risk Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg n=834 participants at risk Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard Care n=334 participants at risk Standard care at onset of migraine attack
General disorders Asthenia/fatigue	9.8% 70/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	13.3% 111/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	13.2% 44/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
General disorders Pain, abdominal	3.4% 24/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	3.2% 27/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.4% 18/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
General disorders Pain, chest	4.8% 34/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	7.3% 61/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	8.4% 28/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Gastrointestinal disorders Diarrhea	3.0% 21/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	3.8% 32/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.4% 18/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Gastrointestinal disorders Nausea	16.5% 117/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	21.3% 178/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	25.7% 86/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Gastrointestinal disorders Vomiting	7.2% 51/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	8.6% 72/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	8.7% 29/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Musculoskeletal and connective tissue disorders Pain, back	4.2% 30/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.8% 48/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.4% 18/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Nervous system disorders Dizziness	9.7% 69/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	16.2% 135/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	10.5% 35/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Nervous system disorders Headache	8.7% 62/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	12.0% 100/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	12.6% 42/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Nervous system disorders Insomnia	3.0% 21/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	3.7% 31/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.1% 17/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Nervous system disorders Paresthesia	4.8% 34/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	7.6% 63/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	7.2% 24/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Nervous system disorders Somnolence	7.0% 50/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	15.2% 127/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	9.0% 30/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Respiratory, thoracic and mediastinal disorders Infection, respiratory, upper	11.0% 78/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	13.7% 114/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	13.8% 46/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Respiratory, thoracic and mediastinal disorders Influenza	6.5% 46/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	6.2% 52/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	7.5% 25/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Respiratory, thoracic and mediastinal disorders Pharyngitis	3.0% 21/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	5.6% 47/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	6.6% 22/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%
Respiratory, thoracic and mediastinal disorders Sinusitis	5.2% 37/711 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	8.6% 72/834 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%	7.8% 26/334 The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) \>1 event. The true overall # of subjects affected w/ only any NonSerious AE \>5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events \<5%