A Study to Describe Pain Intensity, Pain Relief and Safety of Neosaldina in the Treatment of Tension-type Headaches (TTH) in Healthy Participants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03666858
• Collaborator: (none)
• Enrollment: 216
• Locations: 5
• Actual Duration (Months): 8
• Patients Per Site: 43.2
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

The purpose of this study is to describe pain relief in TTH with Neosaldina treatment.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers; Tension-type Headache

Detailed Description

This is an observational, non-interventional and prospective study of healthy participants with episodic TTH who have already been treated with Neosaldina according to regular clinical practice. This study will assess the pain intensity and pain relief of TTH after the uptake of Neosaldina.

This study will enroll approximately 317 participants. All participants will be enrolled into one observational group:

• Neosaldina

Investigators will assess participants from the time of enrolment through the completion of observation period up to 6 months. Each participant will be assessed up to 45 days after first dose. The data will be collected from medical charts and during routine follow up visits. The data from participants will be collected through a self-administered questionnaire using a mobile phone. All the participants will be instructed to insert the data in an application, downloaded in their phone whenever they will have an episode of TTH and use Neosaldina.

This multi-center trial will be conducted in Brazil. The overall duration of observation period in this study is approximately 6 months. Participants will be contacted by telephone on Days 15 and 30 for a follow up and will make a final visit on Day 45.

Study Design

• Study Type: Observational
• Actual Enrollment: 216 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: An Observational, Single-Arm Study to Describe Pain Intensity, Pain Relief and Safety of Neosaldina in the Treatment of Tension-Type Headaches in Healthy Subjects
• Actual Study Start Date: Dec 20, 2018
• Actual Primary Completion Date: Jul 5, 2019
• Actual Study Completion Date: Aug 19, 2019

Arms and Interventions

Arm

Intervention/Treatment

Neosaldina Participants with episodic TTH and who have already been treated with Neosaldina will be included in the observation period of this study. During the observation period, participants will be administered with Neosaldina 2 tablets, orally in the beginning of the TTH episode, every 6 hours, and at maximum of 8 tablets per day, according to regular clinical practice of the physicians. The participants will be observed in this study from Day 1 until Day 45.

Outcome Measures

Primary Outcome Measures

1. Cohort 2: Time-weighted Sum of Pain Intensity Difference From Baseline (0 Hour) to 2 Hours (SPID 0-2) Post-dose [Baseline (0 hour) up to 2 hours post-dose]

   Sum of pain intensity difference (SPID) was calculated as time-weighted sum of the visual analogue scale (VAS) differences over 2 hour period. Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). Pain intensity difference (PID) was the difference between baseline pain intensity (prior to the dosing) and current pain intensity at assessment. Total possible score ranges from -720 (worst) to 120 (best) for SPID 0-2. A higher value in SPID indicated greater pain relief. This outcome was recorded at 15-minutes intervals for the first 60 minutes, followed by 30 minutes from 1 to 2 hours after Neosaldina administration.

Secondary Outcome Measures

1. Cohorts 1 and 2: Percentage of Participants Who Achieved a Reduction of at Least 1 Point Pain in Intensity for Each Time Interval [15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, and 120 minutes]

   Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). Percentage of participants are reported who had no pain relief and who achieved a reduction of at least 1 point pain in intensity for each time interval.

2. Cohorts 1 and 2: Time to Achieve 50 Percent (%) of Pain Intensity Reduction [Each episodic TTH (Day 1 up to Day 45)]

   Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain).

3. Cohorts 1 and 2: Time to First Perceptible Pain Relief (PR) [Each episodic TTH (Day 1 to Day 45)]

   The relief of pain intensity was assessed by the PID% in each time point. Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). PID was the difference between baseline pain intensity (prior to the dosing) and current pain intensity at assessment. Participants evaluated the time to first perceptible relief (confirmed by meaningful relief which was reduction of at least 1 point on pain intensity) according to the pain intensity reported at the time points 0, 15, 30, 45, 60, 90 and 120 minutes after Neosaldina administration.

4. Cohort 1: Mean Duration of PR for Participants With Second Neosaldina Intake [Each episodic TTH (Day 1 up to Day 45)]

   Duration of PR was defined by the time of second intake of study medication.

5. Cohorts 1 and 2: Number of Participants Categorized Based on Treatment Satisfaction According to Patient Global Assessments of Overall Satisfaction [Day 45]

   Overall satisfaction of participants was assessed by the participants based on Patient Global Assessment measured on a 5-point scale for TTH as: 0 (very satisfied); 1 (satisfied); 2 (indifferent); 3 (dissatisfied); 4 (very dissatisfied).

6. Cohorts 1 and 2: Number of Participants Categorized Based on Treatment Satisfaction According to Physician Global Assessments of Overall Satisfaction [Day 45]

   Overall satisfaction of participants was assessed by the physicians based on Physician Global Assessment measured on a 5-point scale for TTH as: 0 (very satisfied); 1 (satisfied); 2 (indifferent); 3 (dissatisfied); 4 (very dissatisfied).

7. Cohort 1: Number of Participants Who Experienced at Least One Adverse Event (AE) After Neosaldina Administration [Day 1 up to Day 45]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Confirmed diagnosis of episodic TTH, as determined by the International Classification of Headache Disorders.

2. Healthy participants who was prescribed 2 tablets of Neosaldina for episodic TTH.

3. Receive treatment according to the Summary of Product Characteristics for Neosaldina.

4. Has access to a mobile phone with the ability to download the app with the study questionnaire.

5. Has at least 1 episode of TTH per month.

Exclusion Criteria:

1. Currently participates or plans to participate in an interventional clinical trial.

2. Has hypersensitivity or intolerance to dypirone (or pyrazolonic derivatives) or other components of the product formula.

3. Has history of migraine, cluster headaches, chronic TTH or any other type of primary headache other than episodic TTH.

4. Has suspected secondary headache.

5. Has serious comorbidities (hypertension, blood dyscrasias, malignant neoplasms, any type of hepatitis or kidney disease, disorders of the hematopoietic system, insufficient function of the bone marrow or certain metabolic diseases, such as hepatic porphyria or congenital deficiency of glucose-6-phosphate dehydrogenase) or taking any medications which might confound the pharmacological effects of the study drug (example immunosuppressive drugs, and beta blockers, anticonvulsivants, antidepressants) within 30 days before the start of study.

6. Women who may be pregnant or breastfeeding during the course of the study.

7. Has history of alcohol abuse or other drugs according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

8. Has mental incapacity, unwillingness or language barriers unable to understand the guidelines specified in this protocol.

9. Any other reason that, in the Investigator's opinion, makes the participant unsuitable to participate in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fundacao do ABC	Santo Andre	SP	Brazil	09060-870
2	Universidade Metropolitana de Santos	Santos	SP	Brazil	11035-050
3	Cemec Centro Multidisciplinar de Estudos Clinicos Ltda-Epp	Sao Bernardo do Campo	SP	Brazil	09715-090
4	Sociedade Brasileira e Japonesa de Beneficencia Santa Cruz	Sao Paulo	SP	Brazil	04122-000
5	Cepic- Centro Paulista de Investigacao Clinica E Servicos Medicos Ltda	Sao Paulo	SP	Brazil	04266-010

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jul 27, 2018
• Statistical Analysis Plan - Oct 4, 2019

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03666858
• Other Study ID Numbers: Neosaldina-5001; U1111-1218-2357
• First Posted: Sep 12, 2018
• Last Update Posted: Jun 2, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy
• Additional relevant MeSH terms: Tension-Type Headache; Headache; Pain

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 5 investigative sites in Brazil from 20 December 2018 to 19 August 2019.
Pre-assignment Detail	Healthy participants with episodic tension-type headache (TTH) who had at least 1 reported headache and Neosaldina intake in mobile phone application enrolled in Cohort 1. Participants from Cohort 1 who had pain intensity reported at 0 and 120 minutes after Neosaldina intake/0 pain before 120 minutes in first headache report enrolled in Cohort 2.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Period Title: Cohort 1
STARTED	216	0
COMPLETED	215	0
NOT COMPLETED	1	0
Period Title: Cohort 1
STARTED	0	138
COMPLETED	0	137
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Cohort 1 (All Participants): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Overall Participants	216
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.56 (11.97)
Sex: Female, Male (Count of Participants)
Female	172 79.6%
Male	44 20.4%
Race/Ethnicity, Customized (Count of Participants)
Asian	9 4.2%
Black or African American	18 8.3%
White	178 82.4%
Unknown or Not Reported	11 5.1%
Region of Enrollment (Count of Participants)
Brazil	216 100%
Occupation (Count of Participants)
Employed	130 60.2%
Employed and student	52 24.1%
Homemaker	13 6%
Student	10 4.6%
Retired	8 3.7%
Unemployed	2 0.9%
Unknown	1 0.5%
Household Income (Count of Participants)
0.5 to 1 minimum wage	4 1.9%
1 to 2 minimum wage	15 6.9%
2 to 3 minimum wage	49 22.7%
3 to 5 minimum wage	43 19.9%
5 to 10 minimum wage	45 20.8%
10 to 20 minimum wage	43 19.9%
20 minimum wage	7 3.2%
Not reported	8 3.7%
No income	1 0.5%
Unknown	1 0.5%

Outcome Measures

1. Primary Outcome

Title	Cohort 2: Time-weighted Sum of Pain Intensity Difference From Baseline (0 Hour) to 2 Hours (SPID 0-2) Post-dose
Description	Sum of pain intensity difference (SPID) was calculated as time-weighted sum of the visual analogue scale (VAS) differences over 2 hour period. Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). Pain intensity difference (PID) was the difference between baseline pain intensity (prior to the dosing) and current pain intensity at assessment. Total possible score ranges from -720 (worst) to 120 (best) for SPID 0-2. A higher value in SPID indicated greater pain relief. This outcome was recorded at 15-minutes intervals for the first 60 minutes, followed by 30 minutes from 1 to 2 hours after Neosaldina administration.
Time Frame	Baseline (0 hour) up to 2 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants from Cohort 1 with TTH who reported at least one headache episode and Neosaldina intake in the mobile phone application during the study and who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report, and with primary endpoint data available.

Arm/Group Title	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	138
Median (Full Range) [units on a scale]	-210

2. Secondary Outcome

Title	Cohorts 1 and 2: Percentage of Participants Who Achieved a Reduction of at Least 1 Point Pain in Intensity for Each Time Interval
Description	Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). Percentage of participants are reported who had no pain relief and who achieved a reduction of at least 1 point pain in intensity for each time interval.
Time Frame	15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, and 120 minutes

Outcome Measure Data

Analysis Population Description

All participants in Cohort(C)1 with TTH who had >=1 headache/Neosaldina intake in mobile application, from C1 in C2 who had pain intensity at 0, 120 minutes after Neosaldina intake,0 pain before 120 minutes in first headache report, with primary endpoint data. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	152	138
At 15 minutes	43.42 20.1%	45.65 NaN
At 30 minutes	27.63 12.8%	28.26 NaN
At 45 minutes	11.18 5.2%	10.87 NaN
At 60 minutes	7.89 3.7%	6.52 NaN
At 90 minutes	2.63 1.2%	5.07 NaN
At 120 minutes	1.32 0.6%	1.45 NaN
No pain relief	5.92 2.7%	2.17 NaN

3. Secondary Outcome

Title	Cohorts 1 and 2: Time to Achieve 50 Percent (%) of Pain Intensity Reduction
Description	Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain).
Time Frame	Each episodic TTH (Day 1 up to Day 45)

Outcome Measure Data

Analysis Population Description

All participants in Cohort (C) 1 with TTH who had >=1 headache/Neosaldina intake in mobile application and from C1 in C2 who had pain intensity at 0, 120 minutes after Neosaldina intake/0 pain before 120 minutes in first headache report, and with primary endpoint data. Overall number analyzed are those who were evaluable for this outcome measure.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	125	132
Mean (Standard Deviation) [minutes]	45.36 (26.63)	51.36 (31.89)

4. Secondary Outcome

Title	Cohorts 1 and 2: Time to First Perceptible Pain Relief (PR)
Description	The relief of pain intensity was assessed by the PID% in each time point. Pain intensity was measured by VAS which was an 11-point numerical rating scale, ranging from 0 (no pain) to 10 (very intense pain). PID was the difference between baseline pain intensity (prior to the dosing) and current pain intensity at assessment. Participants evaluated the time to first perceptible relief (confirmed by meaningful relief which was reduction of at least 1 point on pain intensity) according to the pain intensity reported at the time points 0, 15, 30, 45, 60, 90 and 120 minutes after Neosaldina administration.
Time Frame	Each episodic TTH (Day 1 to Day 45)

Outcome Measure Data

Analysis Population Description

All participants in Cohort (C) 1 with TTH who had >=1 headache/Neosaldina intake in mobile application and from C1 in C2 who had pain intensity at 0, 120 minutes after Neosaldina intake/0 pain before 120 minutes in first headache report, and with primary endpoint data. Overall number analyzed are those who were evaluable for this outcome measure.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	143	135
Mean (Standard Deviation) [minutes]	30.31 (20.57)	31.11 (22.34)

5. Secondary Outcome

Title	Cohort 1: Mean Duration of PR for Participants With Second Neosaldina Intake
Description	Duration of PR was defined by the time of second intake of study medication.
Time Frame	Each episodic TTH (Day 1 up to Day 45)

Outcome Measure Data

Analysis Population Description

All participants with TTH who reported at least one headache episode and Neosaldina intake in the mobile phone application during the study. Here "overall number of participants" analyzed were those who had more than one headache in the same day and were evaluable for this outcome measure.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	6
Mean (Standard Deviation) [hours]	5.16 (2.26)

6. Secondary Outcome

Title	Cohorts 1 and 2: Number of Participants Categorized Based on Treatment Satisfaction According to Patient Global Assessments of Overall Satisfaction
Description	Overall satisfaction of participants was assessed by the participants based on Patient Global Assessment measured on a 5-point scale for TTH as: 0 (very satisfied); 1 (satisfied); 2 (indifferent); 3 (dissatisfied); 4 (very dissatisfied).
Time Frame	Day 45

Outcome Measure Data

Analysis Population Description

All participants in Cohort (C) 1 with TTH who had greater than or equal to (>=1) headache/Neosaldina intake in mobile application and from C1 in C2 who had pain intensity at 0, 120 minutes after Neosaldina intake/0 pain before 120 minutes in first headache report, and with primary endpoint data.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	216	138
Very satisfied	91 42.1%	63 NaN
Satisfied	99 45.8%	59 NaN
Indifferent	6 2.8%	5 NaN
Dissatisfied	7 3.2%	3 NaN
Very dissatisfied	2 0.9%	1 NaN
Unknown	11 5.1%	7 NaN

7. Secondary Outcome

Title	Cohorts 1 and 2: Number of Participants Categorized Based on Treatment Satisfaction According to Physician Global Assessments of Overall Satisfaction
Description	Overall satisfaction of participants was assessed by the physicians based on Physician Global Assessment measured on a 5-point scale for TTH as: 0 (very satisfied); 1 (satisfied); 2 (indifferent); 3 (dissatisfied); 4 (very dissatisfied).
Time Frame	Day 45

Outcome Measure Data

Analysis Population Description

All participants in Cohort (C) 1 with TTH who had >=1 headache/Neosaldina intake in mobile application and from C1 in C2 who had pain intensity at 0, 120 minutes after Neosaldina intake/0 pain before 120 minutes in first headache report, and with primary endpoint data.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina	Cohort 2 (Participants From Cohort 1): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.	All participants from Cohort 1 who reported pain intensity at 0 and 120 minutes after Neosaldina intake or reported 0 pain before 120 minutes in their first headache report and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	216	138
Very satisfied	94 43.5%	62 NaN
Satisfied	98 45.4%	62 NaN
Indifferent	8 3.7%	3 NaN
Dissatisfied	3 1.4%	3 NaN
Very dissatisfied	2 0.9%	1 NaN
Unknown	11 5.1%	7 NaN

8. Secondary Outcome

Title	Cohort 1: Number of Participants Who Experienced at Least One Adverse Event (AE) After Neosaldina Administration
Time Frame	Day 1 up to Day 45

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants with TTH who reported at least one headache episode and Neosaldina intake in the mobile phone application.

Arm/Group Title	Cohort 1 (All Participants): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
Measure Participants	216
Count of Participants [Participants]	6 2.8%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after Day 1 up to Day 45
Adverse Event Reporting Description	AEs are reported for the safety analysis set which included all participants who were enrolled in Cohort 1 with at least one headache report in the mobile phone application during the study. Incidence of adverse events was calculated based on the number of adverse events experienced divided by the total number of participants
Arm/Group Title	Cohort 1 (All Participants): Neosaldina
Arm/Group Description	All healthy participants with at least one TTH episode and who were prescribed with 2 tablets of Neosaldina, orally, at maximum of 8 tablets per day for episodic TTH as per regular clinical practice were enrolled in this observational study on Day 1. Participants were instructed to insert the data in an application, downloaded onto mobile phone, whenever they had an episode of TTH and use Neosaldina. Participants were observed from Day 1 until Day 45. Data were also collected from medical charts and during the routine clinical appointment.
All Cause Mortality
	Cohort 1 (All Participants): Neosaldina
	Affected / at Risk (%)	# Events
Total	0/216 (0%)
Serious Adverse Events
	Cohort 1 (All Participants): Neosaldina
	Affected / at Risk (%)	# Events
Total	0/216 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (All Participants): Neosaldina
	Affected / at Risk (%)	# Events
Total	6/216 (2.8%)
Gastrointestinal disorders
Nausea	1/216 (0.5%)
General disorders
Lack of vitamin D	1/216 (0.5%)
Infections and infestations
Bacterial infection	1/216 (0.5%)
Nervous system disorders
Sleepiness	2/216 (0.9%)
Vascular disorders
Hypertension	1/216 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.