Clinical Trial Results:
A randomized, double-blind, placebo-controlled, parallel arm group study to evaluate the analgesic efficacy and safety of dexketoprofen trometamol and tramadol hydrochloride oral fixed dose combination on moderate to severe acute pain in patients with acute low back pain – DANTE study
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Summary
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EudraCT number |
2019-003656-37 |
Trial protocol |
EE PL ES HU LV HR |
Global end of trial date |
04 May 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jun 2023
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First version publication date |
04 Jun 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MEIN/18/DEX-LBP/001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05170841 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Menarini International Operation Luxembourg SA
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Sponsor organisation address |
1, Avenue de la Gare, Luxembourg, Luxembourg, L-1611
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Public contact |
Clinical Operation Director, Menarini International Operations Luxembourg SA, +39 055 568091, pfabrizzi@menarini.it
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Scientific contact |
Clinical Operation Director, Menarini International Operations Luxembourg SA, +39 055 568091, pfabrizzi@menarini.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 May 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
04 May 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the analgesic efficacy of Desketoprofen/Tramadol fixed combination versus placebo in moderate to severe acute low back pain after the first dose (first 8 hours).
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Protection of trial subjects |
The study was conducted in accordance with the study protocol, the recommendations on biomedical research on human patients of the Declaration of Helsinki, International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, European Union (EU)-Directives and Regulations, and national requirements of the participating countries.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Sep 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 351
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Croatia: 92
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Country: Number of subjects enrolled |
Estonia: 19
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Country: Number of subjects enrolled |
Hungary: 65
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Country: Number of subjects enrolled |
Latvia: 10
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Worldwide total number of subjects |
538
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EEA total number of subjects |
538
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
534
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Study started on 17 September and terminated on 4 May 2022 Number of screened patients: 544 Number of randomized patients: 538 Number of screen failures: 6 patients Number of drop out patients: 14 524 patients completed the study | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Male or female patients aged 18 years to 65 years with acute low back pain of moderate to severe intensity, whose onset of the current acute low back pain episode was within 48 hours prior to Screening. Patients with or without radiculopathy were included, excluding those with neurological signs, according to the Quebec Task Force classification. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Single dose Phase - Period 1
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||
Blinding implementation details |
Double-dummy design was applied to ensure a double-blind condition of DKP.TRIS 25 mg / TRAM.HCl 75 mg versus TRAM.HCl 100 mg versus the respective placebos. The placebo tablets were provided as film-coated tablets with appearance and weight matching relative DKP.TRIS 25 mg / TRAM.HCl 75 mg. The active comparator, TRAM.HCl 100 mg, was provided as 2 capsules of Tramadol 50 mg and, for blinding purpose, 2 capsules of placebo were provided with appearance and weight matching relative Tramadol 50 mg.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Desketoprofen 25mg/Tramadol 75mg | ||||||||||||||||||||||||||||||
Arm description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Desketoprofen/Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1-film-coated tablet orally administered together on Day 1 according to the Investigator’s instructions
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Arm title
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Tramadol 100mg | ||||||||||||||||||||||||||||||
Arm description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
2 capsules orally administered together on Day 1 according to the Investigator’s instructions
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Arm title
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Placebo Desketoprofen/Tramadol | ||||||||||||||||||||||||||||||
Arm description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo Desketoprofen/Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1-film-coated tablet orally administered together on Day 1 according to the Investigator’s instructions
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Arm title
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Placebo Tramadol | ||||||||||||||||||||||||||||||
Arm description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
2 capsules orally administered together on Day 1 according to the Investigator’s instructions
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Period 2
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Period 2 title |
Multiple Dose Phase - Period 2
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Desketoprofen 25mg/Tramadol 75mg | ||||||||||||||||||||||||||||||
Arm description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Desketoprofen/Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1-film-coated tablet orally administered together according to the Investigator’s instructions
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Arm title
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Tramadol 100 mg | ||||||||||||||||||||||||||||||
Arm description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
2 capsules orally administered together according to the Investigator’s instructions
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Arm title
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Desketoprofen 25mg/Tramadol 75mg | ||||||||||||||||||||||||||||||
Arm description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Desketoprofen/Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1-film-coated tablet orally administered together according to the Investigator’s instructions
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Arm title
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Tramadol 100 mg | ||||||||||||||||||||||||||||||
Arm description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tramadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
2 capsules orally administered together according to the Investigator’s instructions
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Baseline characteristics reporting groups
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Reporting group title |
Desketoprofen 25mg/Tramadol 75mg
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tramadol 100mg
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Desketoprofen/Tramadol
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Tramadol
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Modified IIT Population (mIIT)
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The modified intent-to-treat (mITT) population included the first cohort of 510 patients randomized to the 4 treatment arms (204 patients in the DesKetoprofen 25mg/Tramadol 75mg arms + 204 patients in the Tramadol 100mg arms + 51 patients in the Placebo DesKetoprofen/Tramadol arm and 51 patients in the Placebo Tramadol arm) in a 4:4:1:1 ratio.
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Subject analysis set title |
Per Protocol (PP) Population
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per-protocol (PP) population included all patients in the ITT who had not experienced major protocol violations that could affect the primary efficacy analysis. Protocol violations which had a major distorting influence on the primary endpoints resulted in patients being excluded from the PP population (465 patients totally). The PDs identified during the clinical conduct of the study, as authorised in the final PD log, were taken into consideration in the final assignment of patients to the analysis sets. Patients were assigned to the treatment received, for each category in case the treatment received differs from that randomized.
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End points reporting groups
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Reporting group title |
Desketoprofen 25mg/Tramadol 75mg
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions. | ||
Reporting group title |
Tramadol 100mg
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||
Reporting group title |
Placebo Desketoprofen/Tramadol
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||
Reporting group title |
Placebo Tramadol
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Reporting group description |
In the single-dose phase (Period 1), the patients received a single-dose treatment, consisted of 1-film-coated tablet and 2 capsules which were orally administered together at the same time on Day 1 according to the Investigator’s instructions | ||
Reporting group title |
Desketoprofen 25mg/Tramadol 75mg
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Reporting group description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||
Reporting group title |
Tramadol 100 mg
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Reporting group description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||
Reporting group title |
Desketoprofen 25mg/Tramadol 75mg
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Reporting group description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||
Reporting group title |
Tramadol 100 mg
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Reporting group description |
The multiple-dose phase (Period 2) began 8 h after the first dose. The patients assigned to Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg during the single-dose phase continued to receive the same treatment during the multiple-dose phase; however, the patients assigned to receive placebo during the single-dose phase either received Desketoprofen 25mg/Tramadol 75mg fixed combination or Tramadol 100mg every 8 h during the multiple-dose phase. A total of 12 doses of study treatment were administered, with the last study medication intake administered within Day 5 | ||
Subject analysis set title |
Modified IIT Population (mIIT)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The modified intent-to-treat (mITT) population included the first cohort of 510 patients randomized to the 4 treatment arms (204 patients in the DesKetoprofen 25mg/Tramadol 75mg arms + 204 patients in the Tramadol 100mg arms + 51 patients in the Placebo DesKetoprofen/Tramadol arm and 51 patients in the Placebo Tramadol arm) in a 4:4:1:1 ratio.
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Subject analysis set title |
Per Protocol (PP) Population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol (PP) population included all patients in the ITT who had not experienced major protocol violations that could affect the primary efficacy analysis. Protocol violations which had a major distorting influence on the primary endpoints resulted in patients being excluded from the PP population (465 patients totally). The PDs identified during the clinical conduct of the study, as authorised in the final PD log, were taken into consideration in the final assignment of patients to the analysis sets. Patients were assigned to the treatment received, for each category in case the treatment received differs from that randomized.
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End point title |
Time to first achieve an NRS-PI score < 4 or a pain intensity reduction of ≥ 30% from drug intake till 8 h after the first dose (t8h) [1] | ||||||||||||||||
End point description |
To evaluate the analgesic efficacy of Desketoprofen 25mg/Tramadol 75mg fixed combination versus placebo in moderate to severe acute Low Back Pain during the Single Dose Phase - Period 1 (first 8 h after first intake).
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End point type |
Primary
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End point timeframe |
From T=0 to T=8h
|
||||||||||||||||
| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desk/Tram vs placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis. Time to first achieve an NRS-PI score < 4 or a pain intensity reduction of ≥ 30% from drug intake of Desketoprofen 25mg/Tramadol 75mg vs Placebo Desketoprofen/Tramadol and Placebo Tramadol 8 h after the first dose intake. Analysis conducted in the mIIT Population.
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.566 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||
End point title |
Total pain relief vs Tramadol at 4h [2] | ||||||||||||
End point description |
Total pain relief (TOTPAR) at 4 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=4h
|
||||||||||||
| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Tramadol 100mg v Desketoprofen 25mg/Tramadol 75mg
|
||||||||||||
Number of subjects included in analysis |
406
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.013 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
Tot par vs Tramadolo at 6h [3] | ||||||||||||
End point description |
Total pain relief (TOTPAR) at 6 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=6h
|
||||||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
407
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.006 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
Tot par vs Tramadolo 8h [4] | ||||||||||||
End point description |
Total pain relief (TOTPAR) at 8 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||
| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis.
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
408
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.013 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||||||
End point title |
Tot Par vs Placebo at 6h [5] | ||||||||||||||||
End point description |
Total pain relief (TOTPAR) at 6 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=6h
|
||||||||||||||||
| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis.
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.031 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||||||
End point title |
Tot Par vs Placebo at 8h [6] | ||||||||||||||||
End point description |
Total pain relief (TOTPAR) at 8h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||||||
| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadolo vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.027 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||
End point title |
% Patients achieving at least 50% Max TotPar vs Tramadolo at 4h [7] | ||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 4 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Tramadol 100mg arm (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=4h
|
||||||||||||
| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
408
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
% patients achieving at least 50% Max Totpar vs Tramadolo at 6h [8] | ||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 6 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Tramadol 100mg arm (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=6h
|
||||||||||||
| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis.
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
408
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
% Patinets achieving at least 50% of Max TotPar vs Tramadolo at 8h [9] | ||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 8 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Tramadol 100mg arm (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||
| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
408
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||||||
End point title |
% Patients achieving at least 50% of Max TOTPAR vs Placebo at 4h [10] | ||||||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 4 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Placebo arms (Single Dose Phase - Period 1)
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=4h
|
||||||||||||||||
| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.01 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||||||
End point title |
% Patients achieving at least 50% of Max TOTPAR vs Placebo at 6h [11] | ||||||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 6 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Placebo arms (Single Dose Phase - Period 1)
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=6h
|
||||||||||||||||
| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.004 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||||||
End point title |
% Patients achieving at least 50% of Max TOTPAR vs Placebo at 8h [12] | ||||||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 8 h after the first dose in Desketoprofen 25mg/Tramadol 75mg arm as compared with Placebo arms (Single Dose Phase - Period 1)
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||||||
| Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||||||
Comparison groups |
Placebo Desketoprofen/Tramadol v Desketoprofen 25mg/Tramadol 75mg v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.016 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||
End point title |
% Max Totpar vs Tramadol at 4h [13] | ||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=4h
|
||||||||||||
| Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mTT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
407
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.011 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
% Max Totpar vs Tramadol at 6h [14] | ||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=6h
|
||||||||||||
| Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
407
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.007 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
% Max Totpar vs Tramadol at 8h [15] | ||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Single Dose Phase - Period 1)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||
| Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100mg
|
||||||||||||
Number of subjects included in analysis |
408
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.013 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||||||
End point title |
% Max Totpar vs Placebo at 6h [16] | ||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Single Dose Phase - Period 1)
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From t=0 to T=6h
|
||||||||||||||||
| Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1 ) analysis
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
305
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||||||
End point title |
% Max Totpar vs Placebo at 8h [17] | ||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Single Dose Phase - Period 1)
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From T=0 to T=8h
|
||||||||||||||||
| Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Arms involved in the analysis are not all the ones in the baseline period but alternatively: Desketo/Tramadol (experimental) vs Tramadol or Desketo/Tramadol vs Placebo both in the Single dose Phase (Period 1) or in the Multiple Dose Phase (Period 2) depending on the endpoint calculated. |
|||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Placebo in mIIT Population | ||||||||||||||||
Statistical analysis description |
Single Dose Phase (Period 1) analysis
|
||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Placebo Desketoprofen/Tramadol v Placebo Tramadol
|
||||||||||||||||
Number of subjects included in analysis |
306
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.022 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Confidence interval |
|||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple Dose Phase - Totpar vs Tramadolo at 24h | ||||||||||||||||||||
End point description |
Total pain relief (TOTPAR) at 24 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From T=0 to T=24h
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
494
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.045 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple Dose Phase - Totpar vs Tramadolo at 48h | ||||||||||||||||||||
End point description |
Total pain relief (TOTPAR) at 48 h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From T=0 to T=48
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
499
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.042 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple Dose Phase - Totpar vs Tramadolo at 72h | ||||||||||||||||||||
End point description |
Total pain relief (TOTPAR) at 72h after the first dose. TOTPAR was calculated as the time-weighted sum of the PAR-VRS scores
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From T=0 to T=72h
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
499
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.037 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Max Totpar vs Tramadol at 24h | ||||||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
FromTt=0 to T=24
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
494
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.045 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Max Totpar vs Tramadol at 48h | ||||||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From T=0 to T=48h
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
499
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Max Totpar vs Tramadol at 72h | ||||||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Form T=0 to T=72
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
499
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.027 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Max Totpar vs Tramadol at 96h | ||||||||||||||||||||
End point description |
The max TOTPAR was calculated as the theoretical maximum time-weighted sum of the PAR values for each patient. The maximum possible TOTPAR was the value of TOTPAR that would have been obtained if the patient had a complete pain relief for that observation period (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From t=0 to T=96
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in mIIT Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
500
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.035 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Patients achieving at least 50% of Max TotPar vs Tramadol at 48h | ||||||||||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 48 h after the first dose in the Desketoprofen 25mg/Tramadol 75mg arm as compared with Tramadol 100mg arm (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
T=0 to T= 48h
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo Tramadol/Tramadol in PP Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg
|
||||||||||||||||||||
Number of subjects included in analysis |
465
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Multiple dose Phase - % Patients achieving at least 50% of Max TotPar vs Tramadol at 72h | ||||||||||||||||||||
End point description |
Percentage of patients achieving at least 50% of maximum Total Pain Relief (TOTPAR) at 72 h after the first dose in the Desketoprofen 25mg/Tramadol 75mg arm as compared with Tramadol 100mg arm (Multiple Dose Phase - Period 2)
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From T=0 to T=72h
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Desketo/Tramadol vs Tramadol in PP Population | ||||||||||||||||||||
Statistical analysis description |
Multiple Dose Phase (Period 2) analysis
|
||||||||||||||||||||
Comparison groups |
Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg v Desketoprofen 25mg/Tramadol 75mg v Tramadol 100 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
465
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.019 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Informed consent sing to final visit
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Single Dose Phase - Period 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Multiple Dose Phase - Period 2
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Sep 2021 |
The overall rationale for this amendment is to update the change in the sample size as per the re estimation of sample size and to incorporate the changes provided in erratum dated 19 May 2020.
Main changes introduced:
Downgrade of the Statistical Power from the original 90% to the actual 80%
Reduction of the Sample size to 510 from original 680 patients
Added examples of medications for clarification
Creatinine clearance value defining abnormal renal function is corrected from ≥60 mL/min to ≤60 mL/min
The number of countries where the study is conducted is reduced to 6 from 8; Italy and Lithuania are removed from the list. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
