Trial Outcomes & Findings for Study of the Safety and Effectiveness of NXN-188 for the Treatment of Migraine Headache Without Aura (NCT NCT00959751)

NCT ID: NCT00959751

Last Updated: 2014-07-23

Results Overview

Headache relief at 2 hours post administration defined as reduction from Baseline moderate or severe score to mild or none.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 195 participants
• Primary outcome timeframe: 2 hours
• Results posted on: 2014-07-23

Participant Flow

Study Period - 6 months. First subject screened 28 July 2009, Last subject completed the study 9 February 2010.

Participant milestones

Measure	Placebo 3 x capsules, PRN	NXN-188 600 mg 3 x 200 mg capsules, PRN
Overall Study STARTED	97	98
Overall Study COMPLETED	88	86
Overall Study NOT COMPLETED	9	12

Reasons for withdrawal

Measure	Placebo 3 x capsules, PRN	NXN-188 600 mg 3 x 200 mg capsules, PRN
Overall Study Lost to Follow-up	2	3
Overall Study Consent Withdrawn	0	1
Overall Study Non-compliance to Study Procedures	0	1
Overall Study No migraine headache without aura	7	7

Baseline Characteristics

Study of the Safety and Effectiveness of NXN-188 for the Treatment of Migraine Headache Without Aura

Baseline characteristics by cohort

Measure	NXN-188 n=86 Participants 3 x 200 mg capsules	Placebo n=88 Participants 3 x 0 mg capsules	Total n=174 Participants Total of all reporting groups
Age, Continuous	40.2 years STANDARD_DEVIATION 12.34 • n=5 Participants	38.4 years STANDARD_DEVIATION 12.63 • n=7 Participants	39.3 years STANDARD_DEVIATION 12.49 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	74 Participants n=7 Participants	140 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=5 Participants	13 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=5 Participants	75 Participants n=7 Participants	140 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	19 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	72 Participants n=5 Participants	66 Participants n=7 Participants	138 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	74.94 kg STANDARD_DEVIATION 14.695 • n=5 Participants	74.74 kg STANDARD_DEVIATION 17.066 • n=7 Participants	74.84 kg STANDARD_DEVIATION 15.893 • n=5 Participants
Height	168.33 cm STANDARD_DEVIATION 8.502 • n=5 Participants	165.91 cm STANDARD_DEVIATION 9.960 • n=7 Participants	167.10 cm STANDARD_DEVIATION 9.321 • n=5 Participants
Body Mass Index (BMI)	26.2 kg/m^2 STANDARD_DEVIATION 4.09 • n=5 Participants	27.2 kg/m^2 STANDARD_DEVIATION 5.28 • n=7 Participants	26.7 kg/m^2 STANDARD_DEVIATION 4.74 • n=5 Participants
Type of Migraine Without Aura	86 Participants n=5 Participants	88 Participants n=7 Participants	174 Participants n=5 Participants
Type of Migraine With Aura	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Number of Previous Migraines	1.1 migraine episodes STANDARD_DEVIATION 0.30 • n=5 Participants	1.1 migraine episodes STANDARD_DEVIATION 0.23 • n=7 Participants	1.1 migraine episodes STANDARD_DEVIATION 0.27 • n=5 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: Modified LOCF - Efficacy Evaluable Analysis Set

Headache relief at 2 hours post administration defined as reduction from Baseline moderate or severe score to mild or none.

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Headache Relief (Modified LOCF - Efficacy Evaluable Analysis Set)	42 Participants	30 Participants

PRIMARY outcome

Timeframe: 4 hours

Population: 30 and 42 placebo and NXN-188 subjects, respectivley, experienced headache relief at 2 hours. 41 and 55 placebo and NXN-188 subjects, respectively, experienced headache relief at 4 hours.

Headache recurrence is defined as any subject that experiences headache relief at the given time point (i.e., 2 hours or 4 hours), who did not use rescue medication and who experienced a worsening of their headache to moderate or severe within 24 hours following study drug administration. The denominator is the number of subjects who experienced headache relief at 2 hours/4 hours.

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Headache Recurrence (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Recurrence - 2 hours	3 Participants	6 Participants
Headache Recurrence (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Recurrence - 4 hours	2 Participants	4 Participants

SECONDARY outcome

Timeframe: 72 hours

The Headache Severity Score (HSS) assessment was recorded in the diary by the subject and used the following categories: 0 = no pain; 1 = mild pain; 2 = moderate pain; and, 3 = severe pain

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Headache Relief Based on a 2-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 2 hours	28 Participants	17 Participants
Headache Relief Based on a 2-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 4 hours	45 Participants	26 Participants
Headache Relief Based on a 2-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 24 hours	59 Participants	42 Participants
Headache Relief Based on a 2-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 72 hours	54 Participants	47 Participants

SECONDARY outcome

Timeframe: 72 hours

The Headache Severity Score (HSS) assessment was recorded in the diary by the subject and used the following categories: 0 = no pain; 1 = mild pain; 2 = moderate pain; and, 3 = severe pain

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Headache Relief Based on a 1-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 2 hours	52 Participants	40 Participants
Headache Relief Based on a 1-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 4 hours	63 Participants	46 Participants
Headache Relief Based on a 1-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 24 hours	64 Participants	52 Participants
Headache Relief Based on a 1-Point Reduction From Baseline (Modified LOCF - Efficacy Evaluable Analysis Set) Headache Relief - 72 hours	62 Participants	52 Participants

SECONDARY outcome

Timeframe: 72 hours

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Complete Headache Relief (Efficacy Evaluable Analysis Set) Complete Headache Relief - 2 hours	19 Participants	9 Participants
Complete Headache Relief (Efficacy Evaluable Analysis Set) Complete Headache Relief - 4 hours	35 Participants	19 Participants
Complete Headache Relief (Efficacy Evaluable Analysis Set) Complete Headache Relief - 24 hours	56 Participants	36 Participants
Complete Headache Relief (Efficacy Evaluable Analysis Set) Complete Headache Relief - 72 hours	54 Participants	43 Participants

SECONDARY outcome

Timeframe: 24 Hours

Population: Full Analysis Set includes all subjects in the Safety Population who had at least one post-dose observation for headache severity recorded in his or her diary.

Subjects who do not require rescue medication are censored at the time of their last diary assessment completed up to 24 hours following study drug administration.

Outcome measures

Measure	NXN-188 600 mg n=86 Participants 3 x 200 mg capsules, PRN	Placebo n=88 Participants 3 x 0 mg capsules, PRN
Time (Hours) to First Use of Rescue Medication (Full Analysis Set)	NA Participants who required rescue Median times not estimable by Kaplan-Meier because too few subjects required rescue medication within 25 hrs	NA Participants who required rescue Interval 19.6 to Median times not estimable by Kaplan-Meier because too few subjects required rescue medication within 24 hrs

SECONDARY outcome

Timeframe: 24 hours

Population: Full Analysis Set includes all subjects in the Safety Population who had at least one post-dose observation for headache severity recorded in his or her diary.

Overall evaluation of the study drug was measured with a 4-point scale at 24 hours and used the following categories: 1 = Poor; 2 = Moderate; 3 = Good; and,4 = Excellent

Outcome measures

Measure	NXN-188 600 mg n=86 Participants 3 x 200 mg capsules, PRN	Placebo n=88 Participants 3 x 0 mg capsules, PRN
Overall Evaluation of Study Medication at 24 Hours Post Administration (Full Analysis Set) 1 = Poor	20 Participants	37 Participants
Overall Evaluation of Study Medication at 24 Hours Post Administration (Full Analysis Set) 2 = Moderate	22 Participants	19 Participants
Overall Evaluation of Study Medication at 24 Hours Post Administration (Full Analysis Set) 3 = Good	26 Participants	21 Participants
Overall Evaluation of Study Medication at 24 Hours Post Administration (Full Analysis Set) 4 = Excellent	18 Participants	11 Participants

POST_HOC outcome

Timeframe: 2 - 48 hours

Population: Efficacy Evaluable Analysis Set includes all subjects in the Full Analysis Set with an observed or imputed HSS (using rules predefined in the Statistical Analysis Plan \[SAP\]) at both the 2-hour time point and the 4-hour time point when using the modified LOCF approach

Exploratory Post-hoc Analysis: Sustained complete headache relief is defined as a reduction in headache severity from moderate or severe to absent over all indicated time points.

Outcome measures

Measure	NXN-188 600 mg n=80 Participants 3 x 200 mg capsules, PRN	Placebo n=79 Participants 3 x 0 mg capsules, PRN
Sustained Complete Headache Relief (Efficacy Evaluable Analysis Set) 2-24 hours	17 Participants	8 Participants
Sustained Complete Headache Relief (Efficacy Evaluable Analysis Set) 4-24 hours	32 Participants	18 Participants
Sustained Complete Headache Relief (Efficacy Evaluable Analysis Set) 2-48 hours	16 Participants	8 Participants
Sustained Complete Headache Relief (Efficacy Evaluable Analysis Set) 4-48 hours	29 Participants	18 Participants

Adverse Events

NXN-188 600 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	NXN-188 600 mg n=86 participants at risk 3 x 200 mg capsules, PRN	Placebo n=88 participants at risk 3 x 0 mg capsules, PRN
Nervous system disorders Syncope	0.00% 0/86 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	1.1% 1/88 • Number of events 1 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.

Other adverse events

Measure	NXN-188 600 mg n=86 participants at risk 3 x 200 mg capsules, PRN	Placebo n=88 participants at risk 3 x 0 mg capsules, PRN
Nervous system disorders Somnolence	1.2% 1/86 • Number of events 1 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	2.3% 2/88 • Number of events 2 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
General disorders Chills	2.3% 2/86 • Number of events 2 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	0.00% 0/88 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
Gastrointestinal disorders Nausea	4.7% 4/86 • Number of events 4 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	8.0% 7/88 • Number of events 7 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
Gastrointestinal disorders Abdominal pain upper	2.3% 2/86 • Number of events 2 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	1.1% 1/88 • Number of events 1 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
Nervous system disorders Dizziness	5.8% 5/86 • Number of events 8 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	3.4% 3/88 • Number of events 3 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
Musculoskeletal and connective tissue disorders Sensation of heaviness	2.3% 2/86 • Number of events 3 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	0.00% 0/88 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.
Renal and urinary disorders Proteinuria	2.3% 2/86 • Number of events 2 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.	0.00% 0/88 • Adverse event data were collected throughout the study beginning with the dosing of study drug and ending 15 days (± 2 days) p.a. All AE summaries were restricted to TEAEs, which were defined as those AEs that occurred after dosing and those existing AEs that worsened during the study.

Additional Information

Thomas Lategan, PhD

NeurAxon, Inc.

Phone: 417-673-6697

Email: tlategan@neuraxon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor may request Investigator or Institution not to publish or disclose information related to the clinical study.
• Publication restrictions are in place

Restriction type: OTHER