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Clinical Trial Results:
An exploratory, randomized, double-blind, double-dummy, placebo- and active-controlled Phase II trial to evaluate the efficacy and safety of a topical application of GRT7019 in subjects with chronic pain due to knee osteoarthritis

Summary
EudraCT number	2016-002611-18
Trial protocol	AT DE ES
Global end of trial date	17 Jan 2018

Results information
Results version number	v1(current)
This version publication date	17 Oct 2018
First version publication date	17 Oct 2018
Other versions

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

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Trial information

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Sponsor protocol code

KF7019-01

ISRCTN number

US NCT number

WHO universal trial number (UTN)

U1111-1184-3912

Sponsor organisation name

Grünenthal GmbH

Sponsor organisation address

Zieglerstr. 6, Aachen, Germany, 52078

Public contact

Grünenthal Trial Information Desk, Grünenthal GmbH, 0049 2415693223, Clinical-Trials@grunenthal.com

Scientific contact

Dr. Irmgard Bösl, Grünenthal GmbH, 0049 2415690, Clinical-Trials@grunenthal.com

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

13 Aug 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Jan 2018

Was the trial ended prematurely?

Main objective of the trial

Evaluation of the analgesic efficacy of a once daily application of GRT7019 for 4 weeks compared to placebo.

Protection of trial subjects

The trial was conducted according to ICH-GCP guidelines, the applicable local laws and regulations, and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. Regulatory authorities were notified of the trial as required by national regulations, and where necessary relevant authorization was obtained.

Background therapy

Allowed concomitant treatments included: Acetylsalicylic acid (oral doses less than or equal to 325 mg per day for cardiac prophylaxis). Hypnotics including benzodiazepines and non-benzodiazepines if previously used regularly according to the respective Summary of Product Characteristics (SmPCs) for at least 4 weeks prior to the Enrollment Visit and planned to continue on the same dose regimen throughout the trial. Selective serotonin reuptake inhibitors for the treatment of stable depression if previously used at a controlled, stable dose for at least 3 months prior to Enrollment Visit. Triptans for the treatment of migraine. Transcutaneous electrical nerve stimulation, acupuncture, and other physiotherapy, packs and massages, and psychological support were allowed during the trial, provided that the subjects had been on that therapy for at least 4 weeks prior to the Enrollment Visit and continued to undergo that therapy for the duration of the trials at the same frequency and intensity as before. Packs were only allowed if they did not apply external heat to the subject. For unacceptable pain due to chronic osteoarthritis during the trial, paracetamol tablets (500 mg) were provided as rescue medication to all treatment groups. No rescue medication was allowed during the last 3 days before the Baseline Visit. The maximum total daily dose of paracetamol was 2000 mg during the Washout Phase and after allocation to trial treatment until the Follow-up Visit. During the Treatment Period, paracetamol was not be taken for more than 3 consecutive days at the maximum allowed total daily dose. In the subjects randomized to the diclofenac treatment arm, over-encapsulated pantoprazole 20-mg tablets were provided once daily to prevent gastrointestinal system related injuries/bleeding that could result from the treatment with oral diclofenac.

Evidence for comparator

Diclofenac, an approved drug indicated for use in chronic pain due to osteoarthritis (OA) and recommended in treatment guidelines for OA (McAlindon et al. 2014, American Academy of Orthopaedic Surgeons 2013, Jordan et al. 2003), was selected as active comparator/standard of care to demonstrate assay sensitivity. The use of NSAIDs is also in line with The National Institute for Health and Care Excellence (NICE) recommendations for the pharmacological treatment of OA (NICE 2014). A lidocaine patch (Versatis®) was selected as comparator to fulfill in part the requirements of the draft Guideline on clinical development of fixed combination medicinal products (EMA/CHMP/281825/2015) to test the efficacy and show the tolerability profile of the individual component.

Actual start date of recruitment

12 Jun 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 29

Country: Number of subjects enrolled

Austria: 14

Country: Number of subjects enrolled

Germany: 116

Country: Number of subjects enrolled

Spain: 26

Worldwide total number of subjects

185

EEA total number of subjects

185

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)

117

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 229 subjects signed an informed consent at 29 active sites. 185 of these subjects were allocated to study drug (investigational medicinal product = IMP) and received IMP (46 subjects in the placebo arm, 46 in the GRT7019 arm, 48 in the diclofenac arm, and 45 in the lidocaine topical patch arm).

Screening details

Number of subjects started

229 ^[1]

Number of subjects completed

185

Reason: Number of subjects

Adverse event, non-fatal: 1

Reason: Number of subjects

Consent withdrawn by subject: 10

Reason: Number of subjects

Failure to meet randomization criteria: 31

Reason: Number of subjects

Technical reason: 1

Reason: Number of subjects

Other: 1

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 229 subjects signed an informed consent. 185 subjects received at least one dose of investigational medicinal product.

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, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, Medicated plaster

Routes of administration

Oral use, Topical use

Dosage and administration details

All IMPs were administered in a double-dummy design to maintain the blinding. A placebo patch (matching GRT7019 and lidocaine 5% medicated plaster) was administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. Placebo patches, approximately 14 x 10 cm, should have been administered in the morning at a time suitable to accommodate the subjects’ needs and had to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

GRT7019

Arm description

A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

Arm type

Experimental

Investigational medicinal product name

GRT7019

Investigational medicinal product code

Other name

Pharmaceutical forms

Medicated plaster

Routes of administration

Topical use

Dosage and administration details

All IMPs were administered in a double-dummy design to maintain the blinding. GRT7019 patches were administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. The patches, approximately 14 x 10 cm, should have been administered in the morning at a time suitable to accommodate the subjects’ needs and had to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

Diclofenac

Arm description

Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.

Arm type

Active comparator

Investigational medicinal product name

Diclofenac

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

All IMPs were administered in a double-dummy design to maintain the blinding. A diclofenac capsule (containing 62.5 mg sustained-release and 12.5 mg immediate-release diclofenac sodium) was administered orally twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. Over-encapsulated pantoprazole 20-mg tablets were taken once daily to prevent gastrointestinal system related injuries/bleeding that could result from the treatment with oral diclofenac. A placebo patch (matching GRT7019 and lidocaine 5% medicated plaster) was administered once daily for 4 weeks with a wearing time of up to 18 hours but not less than 11 hours. Placebo patches should have been administered in the morning at a time suitable to accommodate the subjects’ needs and must be fixed at the bent knee with an elastic mesh bandage.

Lidocaine 5% medicated plaster

Arm description

Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

Arm type

Active comparator

Investigational medicinal product name

Lidocaine 5% medicated plaster

Investigational medicinal product code

Other name

Versatis

Pharmaceutical forms

Medicated plaster

Routes of administration

Topical use

Dosage and administration details

Lidocaine 5% medicated plasters were applied once daily for 4 weeks with a wearing time of up to 18 hours and a minimum wearing time of 11 hours. Patches should have been administered in the morning to accommodate the subject's needs and were required to be fixed at the bent knee with an elastic mesh bandage. Placebo capsules matching the over-encapsulated diclofenac tablets were administered twice daily, i.e., in the morning (before a meal) and in the evening, for 4 weeks. A placebo capsule matching pantoprazole tablets was taken once daily in the morning for 4 weeks.

Number of subjects in period 1	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Started	46	46	48	45
Completed	41	42	39	42
Not completed	5	4	9	3
Consent withdrawn by subject	-	2	3	1
Adverse event, non-fatal	2	1	2	-
Missing	2	-	2	2
Technical reason	-	-	1	-
Protocol deviation	1	1	-	-
Lack of efficacy	-	-	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

Reporting group title

GRT7019

Reporting group description

A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

Reporting group title

Diclofenac

Reporting group description

Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.

Reporting group title

Lidocaine 5% medicated plaster

Reporting group description

Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

Reporting group values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster	Total
Number of subjects	46	46	48	45	185
Age categorical
Units: Subjects
Adults (18-64 years)	31	26	29	31	117
Adults (65-84 years)	15	20	19	14	68
Age continuous
Units: years
arithmetic mean (standard deviation)	61.2 ( 8.0 )	63.4 ( 7.5 )	61.2 ( 8.6 )	60.7 ( 9.0 )	-
Gender categorical
Units: Subjects
Female	27	30	36	28	121
Male	19	16	12	17	64
Race
Units: Subjects
White	45	46	48	44	183
American Indian or Alaska Native	1	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	1	1
Height
Units: meter
arithmetic mean (standard deviation)	1.707 ( 0.089 )	1.68 ( 0.095 )	1.672 ( 0.08 )	1.708 ( 0.091 )	-
Weight
Units: kilogram(s)
arithmetic mean (standard deviation)	83.1 ( 13.9 )	83.1 ( 13.6 )	83.0 ( 12.3 )	83.1 ( 15.4 )	-
Body Mass Index
Units: kilogram(s)/square meter
arithmetic mean (standard deviation)	28.4 ( 3.6 )	29.3 ( 3.5 )	29.8 ( 4.2 )	28.4 ( 3.7 )	-
WOMAC index score
The WOMAC index score was calculated for the Full Analysis Set by summarizing the scores for the pain, stiffness and physical function subscales (as described by McConnel S, Kolopack P, Davis AM. The Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001; 45(5):453-61.)
Units: units on a scale
arithmetic mean (standard deviation)	NA ( NA )	NA ( NA )	NA ( NA )	NA ( NA )	-
Baseline pain intensity
Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensities were assessed by the subject in an eDiary twice daily (in the morning and the evening) using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine).
Units: units on a scale
arithmetic mean (standard deviation)	NA ( NA )	NA ( NA )	NA ( NA )	NA ( NA )	-
History of osteoarthritis
Answer to the question: "When were you diagnosed with OA of the knee?"
Units: years
arithmetic mean (standard deviation)	9.0 ( 8.4 )	9.7 ( 8.3 )	11.5 ( 10.8 )	11.0 ( 9.8 )	-

Subject analysis set title

Placebo FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

GRT7019 FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

Diclofenac FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

Lidocaine 5% medicated plaster FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis sets values	Placebo FAS	GRT7019 FAS	Diclofenac FAS	Lidocaine 5% medicated plaster FAS
Number of subjects	46	45	47	45
Age categorical
Units: Subjects
Adults (18-64 years)	31	26	29	31
Adults (65-84 years)	15	19	18	14
Age continuous
Units: years
arithmetic mean (standard deviation)	61.2 ( 8.0 )	63.3 ( 7.5 )	61.0 ( 8.7 )	60.7 ( 9.0 )
Gender categorical
Units: Subjects
Female	27	29	35	28
Male	19	16	12	17
Race
Units: Subjects
White	46	45	47	44
American Indian or Alaska Native	1	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	1
Height
Units: meter
arithmetic mean (standard deviation)	170.7 ( 8.9 )	168.0 ( 9.6 )	167.3 ( 8.1 )	170.8 ( 9.1 )
Weight
Units: kilogram(s)
arithmetic mean (standard deviation)	83.1 ( 13.9 )	83.4 ( 13.5 )	83.2 ( 12.4 )	83.1 ( 15.4 )
Body Mass Index
Units: kilogram(s)/square meter
arithmetic mean (standard deviation)	28.4 ( 3.6 )	29.5 ( 3.5 )	29.8 ( 4.3 )	28.4 ( 3.7 )
WOMAC index score
The WOMAC index score was calculated for the Full Analysis Set by summarizing the scores for the pain, stiffness and physical function subscales (as described by McConnel S, Kolopack P, Davis AM. The Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001; 45(5):453-61.)
Units: units on a scale
arithmetic mean (standard deviation)	50.9 ( 11.3 )	43.5 ( 12.5 )	48.7 ( 11.0 )	49.7 ( 11.0 )
Baseline pain intensity
Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensities were assessed by the subject in an eDiary twice daily (in the morning and the evening) using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine).
Units: units on a scale
arithmetic mean (standard deviation)	5.76 ( 0.93 )	5.59 ( 0.90 )	5.55 ( 0.78 )	5.69 ( 0.98 )
History of osteoarthritis
Answer to the question: "When were you diagnosed with OA of the knee?"
Units: years
arithmetic mean (standard deviation)	NA ( NA )	NA ( NA )	NA ( NA )	NA ( NA )

End points

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Reporting group title

Placebo

Reporting group description

Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

Reporting group title

GRT7019

Reporting group description

A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

Reporting group title

Diclofenac

Reporting group description

Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets.

Reporting group title

Lidocaine 5% medicated plaster

Reporting group description

Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

Subject analysis set title

Placebo FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

GRT7019 FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

Diclofenac FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Subject analysis set title

Lidocaine 5% medicated plaster FAS

Subject analysis set type

Full analysis

Subject analysis set description

The FAS includes all subjects allocated with at least 1 IMP administration and with at least 1 non-missing post-baseline assessment of morning or evening average pain.

Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

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End point title

Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

End point description

The primary endpoint was the change from baseline to Week 4 of the double-blind Treatment Period in the weekly average pain intensity. The baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the morning value of Day 1). Pain intensity was recorded twice daily (morning and evening) using an 11-point Numeric Rating Scale (NRS) with a half-day recall period (where 0 = no pain and 10 = Pain as bad as you can imagine). The weekly average pain was defined as the average of the non-missing weekly average morning and weekly average evening pain intensity assessments per trial week.

End point type

Primary

End point timeframe

Baseline to Week 4 of the double-blind Treatment Period. Subjects used their eDiary to record their current pain intensity between 06:00 h and 09:00 h in the morning and once between 19:00 h and 22:00 h in the evening.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	40 ^[1]	41 ^[2]	39 ^[3]	41 ^[4]
Units: units on a scale
least squares mean (standard error)	-2.03 ( 0.27 )	-1.83 ( 0.27 )	-2.16 ( 0.26 )	-1.44 ( 0.27 )

Notes
[1] - Full Analysis Set
[2] - Full Analysis Set
[3] - Full Analysis Set
[4] - Full Analysis Set

GRT7019 versus placebo

Statistical analysis description

MMRM with fixed effects of pooled sites, treatment, time (in weeks), treatment-by-time interaction, positive expectancy score (of SETS questionnaire), and baseline intensity score. An unstructured covariance matrix is used to model the covariance structure, while denominator degrees of freedom are estimated using the Kenward-Roger approximation. The analysis was performed based on all post-baseline weekly pain intensities using only the observed cases without imputation of missing values.

Comparison groups

GRT7019 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

MMRM

Parameter type

MMRM

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.92

Variability estimate

Standard error of the mean

Dispersion value

0.36

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

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End point title

Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

End point description

The average morning pain intensity is the mean of the morning pain intensities assessed once daily in the morning using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine) and asking the subject to “Please indicate how much osteoarthritis knee pain you have right now by selecting one number". A negative change indicates that there was a decrease in pain. If there were 4 or more missing morning pain intensity assessments in a week, the value for the weekly average morning pain intensity was set to missing.

End point type

Secondary

End point timeframe

Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the morning pain intensity of Day -3 up to the morning value of Day 1), the change was up to 31 days after the start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	46 ^[5]	45 ^[6]	47 ^[7]	45 ^[8]
Units: units on a scale
arithmetic mean (standard deviation)
Change from baseline to Week 1	-1.4 ( 1.2 )	-1.1 ( 1.2 )	-1.5 ( 1.4 )	-1.2 ( 1.4 )
Change from baseline to Week 2	-1.9 ( 1.5 )	-1.7 ( 1.7 )	-2.0 ( 1.8 )	-1.6 ( 1.6 )
Change from baseline to Week 3	-2.1 ( 1.6 )	-1.9 ( 1.8 )	-2.3 ( 1.8 )	-1.6 ( 1.5 )
Change from baseline to Week 4	-2.2 ( 1.6 )	-2.0 ( 1.7 )	-2.2 ( 2.0 )	-1.7 ( 1.5 )

Notes
[5] - Full Analysis Set (N = 45 at Week 1) (N = 44 at Week 2) (N = 41 at Week 3) (N = 40 at Week 4)
[6] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 42 at Week 3) (N = 41 at Week 4)
[7] - Full Analysis Set (N = 47 at Week 1) (N = 46 at Week 2) (N = 41 at Week 3) (N = 39 at Week 4)
[8] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 44 at Week 3) (N = 42 at Week 4)

No statistical analyses for this end point

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

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End point title

Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

End point description

The average evening pain intensity is the mean of the evening pain intensities assessed once daily in the evening using an 11-point NRS (where 0 = no pain and 10 = pain as bad as you can imagine) and asking the subject to “Please indicate how much osteoarthritis knee pain you have right now by selecting one number.” A negative change indicates that there was a decrease in pain. If there were 4 or more missing evening pain intensity assessments in a week, the value for the weekly average evening pain intensity was set to missing.

End point type

Secondary

End point timeframe

Baseline pain intensity was calculated as the average of the 6 half-day pain intensities prior to first IMP (starting with the evening pain intensity of Day -3 up to the evening value of Day 1), the change was up to 31 days after the start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	46 ^[9]	45 ^[10]	47 ^[11]	45 ^[12]
Units: Units on a scale
arithmetic mean (standard deviation)
Change from baseline to Week 1	-1.5 ( 1.3 )	-0.8 ( 1.4 )	-1.6 ( 1.3 )	-0.9 ( 1.5 )
Change from baseline to Week 2	-2.0 ( 1.4 )	-1.5 ( 1.6 )	-2.2 ( 1.7 )	-1.5 ( 1.7 )
Change from baseline to Week 3	-2.2 ( 1.6 )	-1.8 ( 1.7 )	-2.4 ( 1.8 )	-1.5 ( 1.7 )
Change from baseline to Week 4	-2.2 ( 1.7 )	-1.9 ( 1.6 )	-2.5 ( 2.0 )	-1.6 ( 1.9 )

Notes
[9] - Full Analysis Set (N = 45 at Week 1) (N = 46 at Week 2) (N = 43 at Week 3) (N = 43 at Week 4)
[10] - Full Analysis Set (N = 45 at Week 1) (N = 45 at Week 2) (N = 42 at Week 3) (N = 41 at Week 4)
[11] - Full Analysis Set (N = 47 at Week 1) (N = 46 at Week 2) (N = 43 at Week 3) (N = 40 at Week 4)
[12] - Full Analysis Set (N = 44 at Week 1) (N = 45 at Week 2) (N = 44 at Week 3) (N = 42 at Week 4)

No statistical analyses for this end point

Secondary: Assessment of responder rate

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End point title

Assessment of responder rate

End point description

A subject is listed as responder in the responder status if both sub-criteria ("At least 30% pain reduction at Week 4 on an 11-point NRS" and "Rescue medication intake at most 500 mg") are fulfilled.

End point type

Secondary

End point timeframe

From first dose of investigational medicinal product (IMP) to Week 4 (End of the double-blind Treatment Period).

End point values	Placebo FAS	GRT7019 FAS	Diclofenac FAS	Lidocaine 5% medicated plaster FAS
Number of subjects analysed	46 ^[13]	45 ^[14]	47 ^[15]	45 ^[16]
Units: subjects
Responder	19	19	23	16
Non responder	27	26	24	29
At least 30% pain reduction at Week 4	20	21	24	16
Rescue medication intake at most 500mg	39	36	39	41

Notes
[13] - Full Analysis Set
[14] - Full Analysis Set
[15] - Full Analysis Set
[16] - Full Analysis Set

No statistical analyses for this end point

Secondary: Change from baseline in pain intensity after physical exercise

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End point title

Change from baseline in pain intensity after physical exercise

End point description

Subjects were asked at the investigational site to walk a stair for 1 minute (Andersson et al. 2010). Pain was recorded on an 11-point Numeric Rating Scale (where 0 = no pain to 10 = pain as bad as you can imagine) directly afterwards by asking the question "Please indicate how much osteoarthritis knee pain you have right now by selecting one number". A negative change in pain intensity score indicates that there has been a decrease in pain from baseline.

End point type

Secondary

End point timeframe

At Final Visit 29 days after starting treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	44 ^[17]	43 ^[18]	42 ^[19]	45 ^[20]
Units: units of a scale
arithmetic mean (standard deviation)	-2.0 ( 2.1 )	-2.2 ( 1.9 )	-2.2 ( 2.2 )	-1.5 ( 2.3 )

Notes
[17] - Full Analysis Set
[18] - Full Analysis Set
[19] - Full Analysis Set
[20] - Full Analysis Set

No statistical analyses for this end point

Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

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End point title

Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

End point description

The average daily rescue medication intake was calculated from the information captured in the eDiary reported in Week 4. In case of missing diary information, a day was imputed with 500 mg paracetamol intake.

End point type

Secondary

End point timeframe

Final Visit 29 days after start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	43 ^[21]	42 ^[22]	42 ^[23]	44 ^[24]
Units: milligram(s)/24 hours
arithmetic mean (standard deviation)	150.5 ( 368.9 )	177.4 ( 359.0 )	101.2 ( 301.0 )	119.3 ( 333.6 )

Notes
[21] - Full Analysis Set
[22] - Full Analysis Set
[23] - Full Analysis Set
[24] - Full Analysis Set

No statistical analyses for this end point

Secondary: Changes from baseline in Western Ontario McMaster Score

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End point title

Changes from baseline in Western Ontario McMaster Score

End point description

The WOMAC is a valid, reliable, and responsive measure of outcome in knee OA (Roos et al. 1999). The WOMAC version used was the WOMAC™ LK3.1, 5-point Likert format. The WOMAC was chosen as a complementary assessment of efficacy. The scores of the 3 subscales pain, stiffness, physical function and the WOMAC index score were calculated. Each of the 5 response categories was assigned a numerical value (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = extreme). Each WOMAC subscale score was calculated by a simple summation of the assigned values scored on the items. The WOMAC index score was calculated by summating the scores for the 3 subscales (McConnel et al. 2001). A negative value indicates that there has been an improvement since baseline.

End point type

Secondary

End point timeframe

Final Visit 29 days after the start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	44 ^[25]	43 ^[26]	43 ^[27]	45 ^[28]
Units: units on a scale
arithmetic mean (standard deviation)
Change in WOMAC Index Score	-17.8 ( 15.7 )	-13.9 ( 13.1 )	-20.3 ( 15.1 )	-15.9 ( 15.7 )
Change in WOMAC Subscale Pain	-4.1 ( 3.7 )	-3.7 ( 3.2 )	-4.6 ( 3.5 )	-3.6 ( 3.3 )
Change in WOMAC Subscale Stiffness	-1.5 ( 1.7 )	-1.0 ( 1.6 )	-1.7 ( 1.3 )	-1.2 ( 1.6 )
Change in WOMAXC Subscale Physical Function	-12.2 ( 11.5 )	-9.2 ( 9.8 )	-13.9 ( 11.5 )	-11.0 ( 11.9 )

Notes
[25] - Full Analysis Set
[26] - Full Analysis Set
[27] - Full Analysis Set
[28] - Full Analysis Set

No statistical analyses for this end point

Secondary: Patient Global Impression of Change (PGIC)

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End point title

Patient Global Impression of Change (PGIC)

End point description

Patient Global Impression of Change used a 7-point scale at Final Visit. The subject was asked to respond by indicating which category fitted best to the question: "Since the start of the study, my overall status is": “Very much improved”, “Much improved”, “Minimally improved", ”No change” , “Minimally worse”, “Much worse”, or “Very much worse”.

End point type

Secondary

End point timeframe

Final Visit 29 Days after starting treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	46 ^[29]	45 ^[30]	47 ^[31]	45 ^[32]
Units: subjects
Very much improved	2	3	9	5
Much improved	13	12	17	12
Minimally improved	18	22	10	14
No change	9	6	5	11
Minimally worse	1	0	1	3
Much worse	1	0	0	0
Very much worse	0	0	0	0
Missing	2	2	5	0

Notes
[29] - Full Analysis Set
[30] - Full Analysis Set
[31] - Full Analysis Set
[32] - Full Analysis Set

No statistical analyses for this end point

Secondary: Clinician’s Global Impression of Change (CGIC)

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End point title

Clinician’s Global Impression of Change (CGIC)

End point description

The Clinician's Global Impression of Change used a 7-point scale at Final Visit. The clinician was asked to respond by indicating which category fitted best to the question: "Compared with the patient’s condition at Baseline, how has it changed?": “Very much improved”, “Much improved”, “Minimally improved", ”No change” , “Minimally worse”, “Much worse”, or “Very much worse”.

End point type

Secondary

End point timeframe

Final Visit 29 days after start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	46 ^[33]	45 ^[34]	47 ^[35]	45 ^[36]
Units: subjects
Very much improved	2	3	9	1
Much improved	16	15	19	16
Minimally improved	14	16	9	13
No change	9	9	6	13
Minimally worse	2	0	0	2
Much worse	1	0	0	0
Very much worse	0	0	0	0
Missing	2	2	4	0

Notes
[33] - Full Analysis Set
[34] - Full Analysis Set
[35] - Full Analysis Set
[36] - Full Analysis Set

No statistical analyses for this end point

Secondary: Incidence of treatment emergent adverse events

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End point title

Incidence of treatment emergent adverse events

End point description

The number of subjects were categorized by the number of Treatment Emergent Adverse Events (none, one, two, three, four, five or more than 5 TEAEs).

End point type

Secondary

End point timeframe

Final Follow-up Visit 31 days after start of treatment.

End point values	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Number of subjects analysed	46 ^[37]	46 ^[38]	48 ^[39]	45 ^[40]
Units: subjects
No TEAEs	30	34	27	29
One TEAE	10	8	15	13
Two TEAEs	6	3	6	3
Three TEAEs	0	1	0	0
Four TEAEs	0	0	0	0
Five TEAEs	0	0	0	0
More than 5 TEAEs	0	0	0	0

Notes
[37] - Safety Set
[38] - Safety Set
[39] - Safety Set
[40] - Safety Set

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment Emergent Adverse Events (TEAEs) reported include all Adverse Events occuring after first topical application or oral intake of investigational medicinal product (IMP) up to and including Visit 7 (Follow-up visit, i.e. scheduled for Day 31).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo

Reporting group description

Placebo patches (matching GRT7019 and lidocaine 5% medicated plasters) and placebo capsules (matching over-encapsulated diclofenac sodium tablets)

Reporting group title

GRT7019

Reporting group description

A fixed-dose combination patch containing 5% lidocaine (700 mg) and 1.3% diclofenac epolamine (182 mg)

Reporting group title

Diclofenac

Reporting group description

Over-encapsulated diclofenac sodium sustained-release (62.5 mg)/immediate-release (12.5 mg) tablets

Reporting group title

Lidocaine 5% medicated plaster

Reporting group description

Versatis® (lidocaine 5% medicated plaster, containing 700 mg lidocaine)

Serious adverse events	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 46 (2.17%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	GRT7019	Diclofenac	Lidocaine 5% medicated plaster
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 46 (32.61%)	11 / 46 (23.91%)	21 / 48 (43.75%)	16 / 45 (35.56%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	1	1	0
General disorders and administration site conditions
Application site erythema
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Application site haematoma
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Application site haemorrhage
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Application site pruritus
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	1 / 45 (2.22%)
occurrences all number	0	0	1	1
Application site reaction
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Application site warmth
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Malaise
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Peripheral swelling
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Catarrh
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Investigations
Blood creatine increased
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	1	1	0
Glomerular filtration rate decreased
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	2 / 48 (4.17%)	1 / 45 (2.22%)
occurrences all number	0	1	2	1
Injury, poisoning and procedural complications
Intentional overdose
subjects affected / exposed	3 / 46 (6.52%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	3	0	0	0
Ligament sprain
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Procedural pain
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Tendon rupture
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Headache
subjects affected / exposed	1 / 46 (2.17%)	1 / 46 (2.17%)	1 / 48 (2.08%)	1 / 45 (2.22%)
occurrences all number	1	1	1	1
Paraesthesia
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	2	0	0	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Abdominal pain
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	2 / 48 (4.17%)	0 / 45 (0.00%)
occurrences all number	1	0	2	0
Abdominal pain upper
subjects affected / exposed	2 / 46 (4.35%)	2 / 46 (4.35%)	1 / 48 (2.08%)	1 / 45 (2.22%)
occurrences all number	2	2	1	1
Diarrhoea
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	2 / 48 (4.17%)	1 / 45 (2.22%)
occurrences all number	1	0	2	1
Dyspepsia
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Faeces soft
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Gastrointestinal pain
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Haematochezia
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Toothache
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Vomiting
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Skin and subcutaneous tissue disorders
Dandruff
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Erythema
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Petechiae
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	1	0	0
Pruritus
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Urticaria
subjects affected / exposed	0 / 46 (0.00%)	1 / 46 (2.17%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	0	2	0	0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	5 / 48 (10.42%)	1 / 45 (2.22%)
occurrences all number	1	0	5	1
Bronchitis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Cystitis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Gastroenteritis
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Influenza
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	0	1
Pneumonia
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	1 / 48 (2.08%)	0 / 45 (0.00%)
occurrences all number	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 46 (2.17%)	0 / 46 (0.00%)	0 / 48 (0.00%)	0 / 45 (0.00%)
occurrences all number	1	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 46 (0.00%)	0 / 46 (0.00%)	0 / 48 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	0	0	3

More information

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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.

None reported

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Clinical trials

Clinical Trial Results:
An exploratory, randomized, double-blind, double-dummy, placebo- and active-controlled Phase II trial to evaluate the efficacy and safety of a topical application of GRT7019 in subjects with chronic pain due to knee osteoarthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

Secondary: Assessment of responder rate

Secondary: Assessment of responder rate

Secondary: Change from baseline in pain intensity after physical exercise

Secondary: Change from baseline in pain intensity after physical exercise

Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

Secondary: Changes from baseline in Western Ontario McMaster Score

Secondary: Changes from baseline in Western Ontario McMaster Score

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Clinician’s Global Impression of Change (CGIC)

Secondary: Clinician’s Global Impression of Change (CGIC)

Secondary: Incidence of treatment emergent adverse events

Secondary: Incidence of treatment emergent adverse events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
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Clinical trials

Clinical Trial Results: An exploratory, randomized, double-blind, double-dummy, placebo- and active-controlled Phase II trial to evaluate the efficacy and safety of a topical application of GRT7019 in subjects with chronic pain due to knee osteoarthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

Primary: Change from baseline to week 4 of the double-blind treatment period in the weekly average pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

Secondary: Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity

Secondary: Assessment of responder rate

Secondary: Assessment of responder rate

Secondary: Change from baseline in pain intensity after physical exercise

Secondary: Change from baseline in pain intensity after physical exercise

Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

Secondary: Average daily rescue medication intake during Week 4 of the double-blind Treatment Period

Secondary: Changes from baseline in Western Ontario McMaster Score

Secondary: Changes from baseline in Western Ontario McMaster Score

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Patient Global Impression of Change (PGIC)

Secondary: Clinician’s Global Impression of Change (CGIC)

Secondary: Clinician’s Global Impression of Change (CGIC)

Secondary: Incidence of treatment emergent adverse events

Secondary: Incidence of treatment emergent adverse events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An exploratory, randomized, double-blind, double-dummy, placebo- and active-controlled Phase II trial to evaluate the efficacy and safety of a topical application of GRT7019 in subjects with chronic pain due to knee osteoarthritis