Download PDF

Clinical Trial Results:
Effect of granisetron on facial skin sensitivity in healthy volunteers

Summary
EudraCT number	2013-000026-57
Trial protocol	SE
Global end of trial date	01 Nov 2018

Results information
Results version number	v1(current)
This version publication date	04 Apr 2021
First version publication date	04 Apr 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

Gra-sensv1

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Karolinska Institutet

Sponsor organisation address

17177, Stockholm, Sweden,

Public contact

Department of Dental medicine Malin Ernberg, Karolinska Institutet, 46 852488236, malin.ernberg@ki.se

Scientific contact

Department of Dental medicine Malin Ernberg, Karolinska Institutet, 46 852488236, malin.ernberg@ki.se

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Nov 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Nov 2018

Global end of trial reached?

Yes

Global end of trial date

01 Nov 2018

Was the trial ended prematurely?

Main objective of the trial

To investigate the effect of granisetron on facial skin sensitivity. To clairify, this is a cross-over study with 3 arms, where the same 18 participants have been included in all 3 arms. This system is not made for the reporting of cross-over studies, therefore workarounds have been made in order to report the results as accurately as possible. Therefore, in the statistics section it looks like there are 36 participants included in each analysis, but the correct should be 18.

Protection of trial subjects

The study was reviewed and approved by Regional Ethical Review Board in Stockholm, Sweden (Dnr 2013/932-31/4) Swedish Medical Products Agency (EudoraCT-number 2008-000746-32). The patients/participants provided their written informed consent to participate in this study.

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Mar 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 18

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted at the Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden. Participants were recruited between March 2014 and November 2018. They were recruited by flyers posted at the Department of Dental Medicine, Karolinska Institutet, and at the library of Södertörn University, both in Huddinge, Sweden.

Screening details

Inclusion criteria were: (a) age between 18 and 40 years, (b) good general health, and (c) male sex.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Randomization and distribution of injections were done by one of the researchers not participating in the data collection.

Are arms mutually exclusive

Baseline Granisetron (test-substance)

Arm description

Test was done at baseline before 1ml of granisetron was injected into the skin over the masseter muscle.

Arm type

Experimental

Investigational medicinal product name

Granisetron

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of granisetron was injected into the skin over the masseter muscle.

Baseline Lidocaine (positive control)

Arm description

Test was done at baseline before 1ml of Lidocaine was injected into the skin over the masseter muscle.

Arm type

Active comparator

Investigational medicinal product name

Lidocaine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of lidocaine was injected into the skin over the masseter muscle.

Baseline Isotonic saline (placebo)

Arm description

Test was done at baseline before 1ml of isotonic saline was injected into the skin over the masseter muscle.

Arm type

Placebo

Investigational medicinal product name

Isotonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of sotonic saline was injected into the skin over the masseter muscle.

5min Granisetron (test-substance)

Arm description

Test was done at 5 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Arm type

Experimental

Investigational medicinal product name

Granisetron

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of granisetron was injected into the skin over the masseter muscle.

5min Lidocaine (positive control)

Arm description

Test was done at min 5 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Arm type

Active comparator

Investigational medicinal product name

Lidocaine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of lidocaine was injected into the skin over the masseter muscle.

5min Isotonic saline (placebo)

Arm description

Test was done at min 5 after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Arm type

Placebo

Investigational medicinal product name

Isotonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of sotonic saline was injected into the skin over the masseter muscle.

20min Granisetron (test-substance)

Arm description

Test was done at 20 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Arm type

Experimental

Investigational medicinal product name

Granisetron

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of granisetron was injected into the skin over the masseter muscle.

20min Lidocaine (positive control)

Arm description

Test was done at min 20 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Arm type

Active comparator

Investigational medicinal product name

Lidocaine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of lidocaine was injected into the skin over the masseter muscle.

20min Isotonic saline (placebo)

Arm description

Test was done at 20 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Arm type

Placebo

Investigational medicinal product name

Isotonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of sotonic saline was injected into the skin over the masseter muscle.

40min Granisetron (test-substance)

Arm description

Test was done at 40 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Arm type

Experimental

Investigational medicinal product name

Granisetron

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of granisetron was injected into the skin over the masseter muscle.

40min Lidocaine (positive control)

Arm description

Test was done at 40 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Arm type

Active comparator

Investigational medicinal product name

Lidocaine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of lidocaine was injected into the skin over the masseter muscle.

40min Isotonic saline (placebo)

Arm description

Test was done at 40 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Arm type

Placebo

Investigational medicinal product name

Isotonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of sotonic saline was injected into the skin over the masseter muscle.

60min Granisetron (test-substance)

Arm description

Test was done at 60 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Arm type

Experimental

Investigational medicinal product name

Granisetron

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of granisetron was injected into the skin over the masseter muscle.

60min Lidocaine (positive control)

Arm description

Test was done at 60 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Arm type

Active comparator

Investigational medicinal product name

Lidocaine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of lidocaine was injected into the skin over the masseter muscle.

60min Isotonic saline (placebo)

Arm description

Test was done at 60 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Arm type

Placebo

Investigational medicinal product name

Isotonic saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

1ml of sotonic saline was injected into the skin over the masseter muscle.

Number of subjects in period 1	Baseline Granisetron (test-substance)	Baseline Lidocaine (positive control)	Baseline Isotonic saline (placebo)	5min Granisetron (test-substance)	5min Lidocaine (positive control)	5min Isotonic saline (placebo)	20min Granisetron (test-substance)	20min Lidocaine (positive control)	20min Isotonic saline (placebo)	40min Granisetron (test-substance)	40min Lidocaine (positive control)	40min Isotonic saline (placebo)	60min Granisetron (test-substance)	60min Lidocaine (positive control)	60min Isotonic saline (placebo)
Started	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18
Completed	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18

Baseline characteristics

Top of page

Reporting group title

Baseline Granisetron (test-substance)

Reporting group description

Test was done at baseline before 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

Baseline Lidocaine (positive control)

Reporting group description

Test was done at baseline before 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

Baseline Isotonic saline (placebo)

Reporting group description

Test was done at baseline before 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

5min Granisetron (test-substance)

Reporting group description

Test was done at 5 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

5min Lidocaine (positive control)

Reporting group description

Test was done at min 5 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

5min Isotonic saline (placebo)

Reporting group description

Test was done at min 5 after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

20min Granisetron (test-substance)

Reporting group description

Test was done at 20 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

20min Lidocaine (positive control)

Reporting group description

Test was done at min 20 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

20min Isotonic saline (placebo)

Reporting group description

Test was done at 20 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

40min Granisetron (test-substance)

Reporting group description

Test was done at 40 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

40min Lidocaine (positive control)

Reporting group description

Test was done at 40 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

40min Isotonic saline (placebo)

Reporting group description

Test was done at 40 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

60min Granisetron (test-substance)

Reporting group description

Test was done at 60 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

60min Lidocaine (positive control)

Reporting group description

Test was done at 60 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

60min Isotonic saline (placebo)

Reporting group description

Test was done at 60 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group values	Baseline Granisetron (test-substance)	Baseline Lidocaine (positive control)	Baseline Isotonic saline (placebo)	5min Granisetron (test-substance)	5min Lidocaine (positive control)	5min Isotonic saline (placebo)	20min Granisetron (test-substance)	20min Lidocaine (positive control)	20min Isotonic saline (placebo)	40min Granisetron (test-substance)	40min Lidocaine (positive control)	40min Isotonic saline (placebo)	60min Granisetron (test-substance)	60min Lidocaine (positive control)	60min Isotonic saline (placebo)	Total
Number of subjects	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18
From 65-84 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18	18

End points

Top of page

Reporting group title

Baseline Granisetron (test-substance)

Reporting group description

Test was done at baseline before 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

Baseline Lidocaine (positive control)

Reporting group description

Test was done at baseline before 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

Baseline Isotonic saline (placebo)

Reporting group description

Test was done at baseline before 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

5min Granisetron (test-substance)

Reporting group description

Test was done at 5 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

5min Lidocaine (positive control)

Reporting group description

Test was done at min 5 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

5min Isotonic saline (placebo)

Reporting group description

Test was done at min 5 after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

20min Granisetron (test-substance)

Reporting group description

Test was done at 20 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

20min Lidocaine (positive control)

Reporting group description

Test was done at min 20 after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

20min Isotonic saline (placebo)

Reporting group description

Test was done at 20 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

40min Granisetron (test-substance)

Reporting group description

Test was done at 40 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

40min Lidocaine (positive control)

Reporting group description

Test was done at 40 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

40min Isotonic saline (placebo)

Reporting group description

Test was done at 40 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Reporting group title

60min Granisetron (test-substance)

Reporting group description

Test was done at 60 min after 1ml of granisetron was injected into the skin over the masseter muscle.

Reporting group title

60min Lidocaine (positive control)

Reporting group description

Test was done at 60 min after 1ml of Lidocaine was injected into the skin over the masseter muscle.

Reporting group title

60min Isotonic saline (placebo)

Reporting group description

Test was done at 60 min after 1ml of isotonic saline was injected into the skin over the masseter muscle.

Primary: Mechanical Detection Threshold Granisetron

Top of page

End point title

Mechanical Detection Threshold Granisetron ^[1]

End point description

The MDT was assessed using calibrated von Frey nylon monofilaments (Anesthesiometer, Somedic Sales AB, Hörby, Sweden) exerting bending forces ranging from 0.026 to 110 g according to the stepwise ascending– descending method in order to find the lowest detectable bending force.

End point type

Primary

End point timeframe

Mechanical detection threshold was assessed at baseline (before injection) and 5, 20, 40 and 60 min after injection of Granisetron.

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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	4.156 ( 1.432 )	6.206 ( 2.306 )	5.856 ( 1.986 )	6.172 ( 2.115 )	5.639 ( 2.012 )

Difference in MDT Granisetron Baseline-5min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 5 min.

Comparison groups

Baseline Granisetron (test-substance) v 5min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[2]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[2] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Granisetron Baseline-20min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 20 min.

Comparison groups

20min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[3]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[3] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Granisetron Baseline-40min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 40 min.

Comparison groups

40min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[4]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[4] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Granisetron Baseline-60min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 60 min.

Comparison groups

60min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[5]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[5] - Changes of MDT across times were analyzed using Friedman ANOVA.

Primary: Mechanical Detection Threshold Lidocaine

Top of page

End point title

Mechanical Detection Threshold Lidocaine ^[6]

End point description

End point type

Primary

End point timeframe

Mechanical Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	4.228 ( 1.150 )	9.628 ( 2.417 )	6.950 ( 2.630 )	6.300 ( 2.552 )	5.978 ( 2.437 )

Difference in MDT Lidocaine Baseline-5min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 5 min.

Comparison groups

5min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[7]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[7] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Lidocaine Baseline-20min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 20 min.

Comparison groups

20min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[8]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[8] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Lidocaine Baseline-40min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 5 min.

Comparison groups

40min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[9]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[9] - Changes of CDT, HDT, and MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Lidocaine Baseline-60min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 60 min.

Comparison groups

60min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[10]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[10] - Changes of CDT, HDT, and MDT across times were analyzed using Friedman ANOVA.

Primary: Mechanical Detection Threshold Placebo

Top of page

End point title

Mechanical Detection Threshold Placebo ^[11]

End point description

End point type

Primary

End point timeframe

Mechanical Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Isotonic Saline.

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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	4.222 ( 1.123 )	5.367 ( 1.625 )	5.717 ( 1.860 )	5.411 ( 1.592 )	5.267 ( 1.649 )

Difference in MDT Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 5 min.

Comparison groups

Baseline Isotonic saline (placebo) v 5min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[12]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[12] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Isotonic Saline Baseline-20min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 20 min.

Comparison groups

20min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[13]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[13] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 40 min.

Comparison groups

40min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[14]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[14] - Changes of MDT across times were analyzed using Friedman ANOVA.

Difference in MDT Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Mechanical Detection Threshold from Baseline to 60 min

Comparison groups

60min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[15]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[15] - Changes of MDT across times were analyzed using Friedman ANOVA.

Primary: Mechanical Pain Sensitivity Granisetron

Top of page

End point title

Mechanical Pain Sensitivity Granisetron ^[16]

End point description

In order to assess MPS, the von Frey nylon monofilament 19 with a force of 110 g was used.

End point type

Primary

End point timeframe

Mechanical Pain Sensitivity was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Granisetron.

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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	39.222 ( 16.275 )	30.167 ( 16.176 )	31.556 ( 18.234 )	34.611 ( 16.832 )	35.500 ( 18.066 )

Difference in MPS Granisetron Baseline-5min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 5 min.

Comparison groups

5min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[17]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[17] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Granisetron Baseline-20min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 20 min.

Comparison groups

20min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[18]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[18] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Granisetron Baseline-40min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 40 min.

Comparison groups

40min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[19]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[19] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Granisetron Baseline-60min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 60 min.

Comparison groups

60min Granisetron (test-substance) v Baseline Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

> 0.05

Method

ANOVA

Confidence interval

Primary: Mechanical Pain Sensitivity Lidocaine

Top of page

End point title

Mechanical Pain Sensitivity Lidocaine ^[20]

End point description

In order to assess MPS, the von Frey nylon monofilament 19 with a force of 110 g was used.

End point type

Primary

End point timeframe

Mechanical Pain Sensitivity was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[20] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	38.556 ( 14.468 )	27.556 ( 19.123 )	35.994 ( 16.579 )	39.833 ( 17.130 )	38.333 ( 15.718 )

Difference in MPS Lidocaine Baseline-5min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 5 min.

Comparison groups

5min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[21]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[21] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Lidocaine Baseline-20min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 20 min.

Comparison groups

20min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[22]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[22] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Lidocaine Baseline-40min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 40 min.

Comparison groups

40min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[23]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[23] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Lidocaine Baseline-60min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 60 min.

Comparison groups

60min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[24]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[24] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Primary: Mechanical Pain Sensitivity Placebo

Top of page

End point title

Mechanical Pain Sensitivity Placebo ^[25]

End point description

In order to assess MPS, the von Frey nylon monofilament 19 with a force of 110 g was used.

End point type

Primary

End point timeframe

Mechanical Pain Sensitivity was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocain.

Notes
[25] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	36.111 ( 14.552 )	28.889 ( 16.743 )	32.889 ( 14.336 )	34.389 ( 16.881 )	37.389 ( 16.624 )

Difference in MPS Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 5 min.

Comparison groups

5min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[26]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[26] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Isotonic Saline Baseline-20min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 20 min.

Comparison groups

20min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[27]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[27] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 40 min.

Comparison groups

40min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[28]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[28] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Difference in MPS Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Mechanical Pain Sensitivity (MPS) from Baseline to 60 min.

Comparison groups

60min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[29]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[29] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in MPS.

Primary: Cold Detection Threshold Granisetron

Top of page

End point title

Cold Detection Threshold Granisetron ^[30]

End point description

In order to assess the thermal detection threshold, an electronic thermo-test system was used (CHEPS thermo-test system, Medoc Ltd. Ramat Yishai, Israel). The measurements were done using an advanced thermal stimulator (ATS) with a contact area of 3 × 3 cm that was placed on the skin surface of the masseter. A preset automatic program was used in which the thermal stimulator had a baseline temperature of 32◦C (skin temperature) and a minimum and maximum temperature of 0◦ and 55◦C.

End point type

Primary

End point timeframe

Cold Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Granisetron.

Notes
[30] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	30.021 ( 1.510 )	29.342 ( 2.293 )	29.426 ( 1.621 )	29.513 ( 1.416 )	29.632 ( 1.455 )

Difference in CDT Granisetron Baseline-5min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 5 min.

Comparison groups

Baseline Granisetron (test-substance) v 5min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[31]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[31] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Granisetron Baseline-20min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 20 min.

Comparison groups

Baseline Granisetron (test-substance) v 20min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[32]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[32] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Granisetron Baseline-40min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 40 min.

Comparison groups

Baseline Granisetron (test-substance) v 40min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[33]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[33] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Granisetron Baseline-60min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 60 min.

Comparison groups

Baseline Granisetron (test-substance) v 60min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[34]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[34] - Changes of CDT across times were analyzed using Friedman ANOVA.

Primary: Cold Detection Threshold Lidocaine

Top of page

End point title

Cold Detection Threshold Lidocaine ^[35]

End point description

End point type

Primary

End point timeframe

Cold Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[35] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	31.576 ( 1.947 )	29.103 ( 8.505 )	29.896 ( 5.399 )	30.868 ( 5.121 )	30.567 ( 6.864 )

Difference in CDT Lidocaine Baseline-5min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 5 min.

Comparison groups

5min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[36]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[36] - Changes of CDT across times were analyzed using Friedman ANOVA

Difference in CDT Lidocaine Baseline-20min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 20 min.

Comparison groups

Baseline Lidocaine (positive control) v 20min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[37]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[37] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Lidocaine Baseline-40min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 40 min.

Comparison groups

Baseline Lidocaine (positive control) v 40min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[38]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[38] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Lidocaine Baseline-60min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 60 min.

Comparison groups

Baseline Lidocaine (positive control) v 60min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[39]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[39] - Changes of CDT across times were analyzed using Friedman ANOVA.

Primary: Cold Detection Threshold Isotonic saline

Top of page

End point title

Cold Detection Threshold Isotonic saline ^[40]

End point description

End point type

Primary

End point timeframe

Cold Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Isotonic saline.

Notes
[40] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	30.177 ( 1.309 )	28.967 ( 1.979 )	28.672 ( 2.253 )	28.773 ( 2.614 )	28.808 ( 2.548 )

Difference in CDT Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 5 min.

Comparison groups

Baseline Isotonic saline (placebo) v 5min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[41]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[41] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Isotonic Saline Baseline-20min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 20 min.

Comparison groups

Baseline Isotonic saline (placebo) v 20min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[42]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[42] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 40 min.

Comparison groups

Baseline Isotonic saline (placebo) v 40min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[43]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[43] - Changes of CDT across times were analyzed using Friedman ANOVA.

Difference in CDT Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Cold Detection Threshold (CDT) from Baseline to 60 min.

Comparison groups

Baseline Isotonic saline (placebo) v 60min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[44]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[44] - Changes of CDT across times were analyzed using Friedman ANOVA.

Primary: Heat Detection Threshold Granisetron

Top of page

End point title

Heat Detection Threshold Granisetron ^[45]

End point description

End point type

Primary

End point timeframe

Heat Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Granisetron.

Notes
[45] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	33.967 ( 1.230 )	35.413 ( 2.707 )	34.932 ( 1.633 )	35.319 ( 2.447 )	35.154 ( 2.513 )

Difference in HDT Granisetron Baseline-5min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 5 min.

Comparison groups

Baseline Granisetron (test-substance) v 5min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[46]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[46] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Granisetron Baseline-20min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 20 min.

Comparison groups

Baseline Granisetron (test-substance) v 20min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[47]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[47] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Granisetron Baseline-40min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 40 min.

Comparison groups

Baseline Granisetron (test-substance) v 40min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[48]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[48] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Granisetron Baseline-60min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 60 min.

Comparison groups

Baseline Granisetron (test-substance) v 60min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05 ^[49]

Method

ANOVA

Confidence interval

Notes
[49] - Changes of HDT across times were analyzed using Friedman ANOVA.

Primary: Heat Detection Threshold Lidocaine

Top of page

End point title

Heat Detection Threshold Lidocaine ^[50]

End point description

End point type

Primary

End point timeframe

Heat Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[50] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	34.379 ( 1.973 )	37.723 ( 4.672 )	37.262 ( 4.101 )	36.160 ( 3.829 )	35.885 ( 3.961 )

Difference in HDT Lidocaine Baseline-5min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 5 min.

Comparison groups

Baseline Lidocaine (positive control) v 5min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[51]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[51] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Lidocaine Baseline-20min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 20 min.

Comparison groups

Baseline Lidocaine (positive control) v 20min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[52]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[52] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Lidocaine Baseline-40min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 40 min.

Comparison groups

Baseline Lidocaine (positive control) v 40min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[53]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[53] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Lidocaine Baseline-60min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 60 min.

Comparison groups

Baseline Lidocaine (positive control) v 60min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[54]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[54] - Changes of HDT across times were analyzed using Friedman ANOVA.

Primary: Heat Detection Threshold Isotonic saline

Top of page

End point title

Heat Detection Threshold Isotonic saline ^[55]

End point description

End point type

Primary

End point timeframe

Heat Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocain Isotonic saline.

Notes
[55] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	34.576 ( 1.617 )	35.145 ( 1.869 )	35.518 ( 2.075 )	35.434 ( 1.978 )	35.484 ( 1.728 )

Difference in HDT Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 5 min.

Comparison groups

Baseline Isotonic saline (placebo) v 5min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[56]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[56] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Isotonic Saline Baseline20min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 20 min.

Comparison groups

Baseline Isotonic saline (placebo) v 20min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[57]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[57] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 40 min.

Comparison groups

Baseline Isotonic saline (placebo) v 40min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[58]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[58] - Changes of HDT across times were analyzed using Friedman ANOVA.

Difference in HDT Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Heat Detection Threshold (HDT) from Baseline to 60 min.

Comparison groups

Baseline Isotonic saline (placebo) v 60min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[59]

P-value

< 0.05

Method

ANOVA

Confidence interval

Notes
[59] - Changes of HDT across times were analyzed using Friedman ANOVA.

Primary: Cold Pain Threshold Garnisetron

Top of page

End point title

Cold Pain Threshold Garnisetron ^[60]

End point description

In order to assess the pain threshold, an electronic thermo-test system was used (CHEPS thermo-test system, Medoc Ltd. Ramat Yishai, Israel). The measurements were done using an advanced thermal stimulator (ATS) with a contact area of 3 × 3 cm that was placed on the skin surface of the masseter. A preset automatic program was used in which the thermal stimulator had a baseline temperature of 32◦C (skin temperature) and a minimum and maximum temperature of 0◦ and 55◦C.

End point type

Primary

End point timeframe

Cold Pain Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Granisetron.

Notes
[60] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	18.641 ( 7.776 )	17.151 ( 9.681 )	16.521 ( 8.839 )	18.422 ( 7.783 )	16.708 ( 7.869 )

Difference in CPT Granisetron Baseline-5min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 5 min.

Comparison groups

Baseline Granisetron (test-substance) v 5min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[61]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[61] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Granisetron Baseline-20min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 20 min.

Comparison groups

Baseline Granisetron (test-substance) v 20min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[62]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[62] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Granisetron Baseline-40min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 40 min.

Comparison groups

Baseline Granisetron (test-substance) v 40min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[63]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[63] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Granisetron Baseline-60min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 60 min.

Comparison groups

Baseline Granisetron (test-substance) v 60min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[64]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[64] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Primary: Cold Pain Threshold Lidocaine

Top of page

End point title

Cold Pain Threshold Lidocaine ^[65]

End point description

End point type

Primary

End point timeframe

Cold Pain Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[65] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	15.582 ( 9.676 )	11.533 ( 10.075 )	13.910 ( 8.743 )	15.953 ( 9.560 )	15.063 ( 9.501 )

Difference in CPT Lidocaine Baseline-5min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 5 min.

Comparison groups

5min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[66]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[66] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Lidocaine Baseline-20min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 20 min.

Comparison groups

20min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[67]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[67] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Lidocaine Baseline-40min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 40 min.

Comparison groups

Baseline Lidocaine (positive control) v 40min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[68]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[68] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Lidocaine Baseline-60min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 60 min.

Comparison groups

60min Lidocaine (positive control) v Baseline Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[69]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[69] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Primary: Cold Pain Threshold Isotonic Saline

Top of page

End point title

Cold Pain Threshold Isotonic Saline ^[70]

End point description

End point type

Primary

End point timeframe

Cold Detection Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Isotonic Saline.

Notes
[70] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	19.159 ( 9.211 )	18.714 ( 11.567 )	18.203 ( 10.356 )	16.877 ( 11.491 )	18.029 ( 11.239 )

Difference in CPT Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 5 min.

Comparison groups

Baseline Isotonic saline (placebo) v 5min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[71]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[71] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Isotonic Saline Baseline-20min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 20 min.

Comparison groups

Baseline Isotonic saline (placebo) v 20min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[72]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[72] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 40 min.

Comparison groups

Baseline Isotonic saline (placebo) v 40min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[73]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[73] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Difference in CPT Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Cold Pain Threshold (CPT) from Baseline to 60 min.

Comparison groups

60min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[74]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[74] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in CPT.

Primary: Heat Pain Threshold Granisetron

Top of page

End point title

Heat Pain Threshold Granisetron ^[75]

End point description

End point type

Primary

End point timeframe

Heat Pain Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Granisetron.

Notes
[75] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Granisetron (test-substance)	5min Granisetron (test-substance)	20min Granisetron (test-substance)	40min Granisetron (test-substance)	60min Granisetron (test-substance)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	43.617 ( 4.670 )	44.746 ( 3.826 )	45.190 ( 3.415 )	44.766 ( 3.694 )	44.905 ( 3.776 )

Difference in HPT Granisetron Baseline-5min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 5 min.

Comparison groups

Baseline Granisetron (test-substance) v 5min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[76]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[76] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Granisetron Baseline-20min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 20 min.

Comparison groups

Baseline Granisetron (test-substance) v 20min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[77]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[77] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Granisetron Baseline-40min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 40 min.

Comparison groups

Baseline Granisetron (test-substance) v 40min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[78]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[78] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Granisetron Baseline-60min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 60 min.

Comparison groups

Baseline Granisetron (test-substance) v 60min Granisetron (test-substance)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[79]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[79] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Primary: Heat Pain Threshold Lidocaine

Top of page

End point title

Heat Pain Threshold Lidocaine ^[80]

End point description

End point type

Primary

End point timeframe

Heat Pain Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[80] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Lidocaine (positive control)	5min Lidocaine (positive control)	20min Lidocaine (positive control)	40min Lidocaine (positive control)	60min Lidocaine (positive control)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	43.555 ( 3.814 )	45.378 ( 3.283 )	45.197 ( 2.972 )	44.187 ( 4.176 )	42.361 ( 9.086 )

Difference in HPT Lidocaine Baseline-5min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 5 min.

Comparison groups

Baseline Lidocaine (positive control) v 5min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[81]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[81] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Lidocaine Baseline-20min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 20 min.

Comparison groups

Baseline Lidocaine (positive control) v 20min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[82]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[82] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Lidocaine Baseline-40min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 40 min.

Comparison groups

Baseline Lidocaine (positive control) v 40min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[83]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[83] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Lidocaine Baseline-60min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 60 min.

Comparison groups

Baseline Lidocaine (positive control) v 60min Lidocaine (positive control)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[84]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[84] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Primary: Heat Pain Threshold Isotonic Saline

Top of page

End point title

Heat Pain Threshold Isotonic Saline ^[85]

End point description

End point type

Primary

End point timeframe

Heat Pain Threshold was assessed at baseline (before injection) and 5, 20, 40, 60min after injection of Lidocaine.

Notes
[85] - 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: This is a cross-over study, but this system cannot accommodate this. Therefore, in order to report the results, we have tried to used workarounds, which means there are only total 3 arms, but in order to report the result as accurately as possible, we have created one arm for each variable. That is why not all arms have been used for each end point.

End point values	Baseline Isotonic saline (placebo)	5min Isotonic saline (placebo)	20min Isotonic saline (placebo)	40min Isotonic saline (placebo)	60min Isotonic saline (placebo)
Number of subjects analysed	18	18	18	18	18
Units: Score
arithmetic mean (standard deviation)	42.580 ( 4.770 )	42.801 ( 4.710 )	43.268 ( 4.910 )	43.262 ( 4.897 )	42.931 ( 4.757 )

Difference in HPT Isotonic Saline Baseline-5min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 5 min.

Comparison groups

5min Isotonic saline (placebo) v Baseline Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[86]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[86] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Isotonic Saline Baseline-20min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 20 min.

Comparison groups

Baseline Isotonic saline (placebo) v 20min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[87]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[87] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Isotonic Saline Baseline-40min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 40 min.

Comparison groups

Baseline Isotonic saline (placebo) v 40min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[88]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[88] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Difference in HPT Isotonic Saline Baseline-60min

Statistical analysis description

Difference in Heat Pain Threshold (HPT) from Baseline to 60 min.

Comparison groups

Baseline Isotonic saline (placebo) v 60min Isotonic saline (placebo)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[89]

P-value

> 0.05

Method

ANOVA

Confidence interval

Notes
[89] - Two-way ANOVA for repeated measures (RM ANOVA) with time as factor analyzed group differences in HPT.

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to 60 min after injection.

Assessment type

Non-systematic

Dictionary name

n/a

Dictionary version

n/a

Frequency threshold for reporting non-serious adverse events: 0%

Notes
[1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
Justification: There were no non-serious adverse events, which we also did not have before when we injected granisetron intramuscularly. The adverse events that exist for granisetron i FASS (mosty constipation and headache) mainly applies to systemic administration with higher doses and not a relatively low single dose that we used.

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

There were two researchers performing the examinations and injections. Some of the participants found it difficult to identify the exact transition from non-painful to painful thermal sensation, especially regarding CPT.

http://www.ncbi.nlm.nih.gov/pubmed/32328025

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Effect of granisetron on facial skin sensitivity in healthy volunteers

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mechanical Detection Threshold Granisetron

Primary: Mechanical Detection Threshold Granisetron

Primary: Mechanical Detection Threshold Lidocaine

Primary: Mechanical Detection Threshold Lidocaine

Primary: Mechanical Detection Threshold Placebo

Primary: Mechanical Detection Threshold Placebo

Primary: Mechanical Pain Sensitivity Granisetron

Primary: Mechanical Pain Sensitivity Granisetron

Primary: Mechanical Pain Sensitivity Lidocaine

Primary: Mechanical Pain Sensitivity Lidocaine

Primary: Mechanical Pain Sensitivity Placebo

Primary: Mechanical Pain Sensitivity Placebo

Primary: Cold Detection Threshold Granisetron

Primary: Cold Detection Threshold Granisetron

Primary: Cold Detection Threshold Lidocaine

Primary: Cold Detection Threshold Lidocaine

Primary: Cold Detection Threshold Isotonic saline

Primary: Cold Detection Threshold Isotonic saline

Primary: Heat Detection Threshold Granisetron

Primary: Heat Detection Threshold Granisetron

Primary: Heat Detection Threshold Lidocaine

Primary: Heat Detection Threshold Lidocaine

Primary: Heat Detection Threshold Isotonic saline

Primary: Heat Detection Threshold Isotonic saline

Primary: Cold Pain Threshold Garnisetron

Primary: Cold Pain Threshold Garnisetron

Primary: Cold Pain Threshold Lidocaine

Primary: Cold Pain Threshold Lidocaine

Primary: Cold Pain Threshold Isotonic Saline

Primary: Cold Pain Threshold Isotonic Saline

Primary: Heat Pain Threshold Granisetron

Primary: Heat Pain Threshold Granisetron

Primary: Heat Pain Threshold Lidocaine

Primary: Heat Pain Threshold Lidocaine

Primary: Heat Pain Threshold Isotonic Saline

Primary: Heat Pain Threshold Isotonic Saline

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Effect of granisetron on facial skin sensitivity in healthy volunteers