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Blood-Oxygen-Level-Dependent (BOLD) responses to painful mechanical stimulation of the OA knee following treatment with four consecutive doses (at 8 hour intervals) on giving sustained released paracetamol treatment or placebo will be compared. The fMRI and pain assessments will occur approximately 2-5 hours after taking the final dose.
The objective of this study is to investigate if functional magnetic response imaging (fMRI) can detect the effects of a known pain medicine at over-the-counter doses in people with osteoarthritis (OA) of the knee. The fMRI is a harmless and painless technique that is used in the current study to collect images of brain activity to see if is changed when feeling pain. In this study, BOLD response to mechanical stimulation via pressure stimuli applied to the tibio-femoral joint and patello-femoral in participants with knee OA following four treatment doses of any of three treatment will be compared.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Paracetamol caplets | Experimental | Two 665 mg sustained release paracetamol caplets administered orally with water. |
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| Placebo caplets | Placebo Comparator | Two placebo caplets administered orally with water. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paracetamol | Drug | 665 mg sustained release paracetamol caplets |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Oxygen Level-Dependent (BOLD) Response in the Tibio-femoral Joint of Knee Osteoarthritis (OA): [BOLD (T-f)] | BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution. | Baseline to 2-5 hours post last dose administration |
| Measure | Description | Time Frame |
|---|---|---|
| BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)] | BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Del Mar | Barcelona | CP: 08003 | Spain |
Out of 33 screened participants, 31 were randomized, while 2 participants were considered as screen failures
Study was conducted at a single centre in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Participants took part in 3 study sessions. Session 1-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 2-no treatment was given. Session 3-participant took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Placebo |
| Drug |
Placebo caplets |
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| Baseline to 2-5 hours post last dose administration |
| Subjective Numerical Rating Scale (NRS) Response for Treatment Effect on OA Knee Before Stimulation: [NRS (TRT)] | Subjective NRS response for each participant was calculated as difference of pre-treatment NRS pain assessment before stimulus and post-treatment NRS pain assessment before stimulus. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | Baseline and post-dose before stimulus |
| Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation Prior the fMRI Scan: [NRS (T-f Pre-scan)] | Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on tibio-femoral joint. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | Baseline and post-dose pre-scan after stimulus |
| Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation Prior the fMRI Scan: [NRS (P-f Pre-scan)] | Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | Baseline and post-dose pre-scan after stimulus |
| Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation After the fMRI Scan: [NRS (T-f Post-scan)] | Subjective NRS response for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on tibio-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | Baseline and post-dose post-scan after stimulus |
| Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)] | Subjective NRS response for each participant for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | Baseline and post-dose post-scan after stimulus |
| FG001 | Sequence 2 | Participants took part in 3 study sessions. Session 1-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 2-no treatment was given. Session 3-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. |
| FG002 | Sequence 3 | Participants took part in 3 study sessions. Session 1-no treatment was given. Session 2-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 3-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered.A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. |
| FG003 | Sequence 4 | Participants took part in 3 study sessions. Session 1-no treatment was given. Session 2-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 3-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. |
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| Wash-out Period 1 |
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| Period 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Total Participants for Baseline Measurement | All randomized participants except one were evaluated for baseline measures. One participant had misallocated treatments that could not be determined. Therefore, this participant was excluded from all populations including safety. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Oxygen Level-Dependent (BOLD) Response in the Tibio-femoral Joint of Knee Osteoarthritis (OA): [BOLD (T-f)] | BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution. | Intention-to-treat (ITT) population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Z-score | Baseline to 2-5 hours post last dose administration |
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| Secondary | BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)] | BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Z-score | Baseline to 2-5 hours post last dose administration |
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| Secondary | Subjective Numerical Rating Scale (NRS) Response for Treatment Effect on OA Knee Before Stimulation: [NRS (TRT)] | Subjective NRS response for each participant was calculated as difference of pre-treatment NRS pain assessment before stimulus and post-treatment NRS pain assessment before stimulus. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and post-dose before stimulus |
| |||||||||||||||||||||||||||||||||
| Secondary | Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation Prior the fMRI Scan: [NRS (T-f Pre-scan)] | Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on tibio-femoral joint. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and post-dose pre-scan after stimulus |
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| Secondary | Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation Prior the fMRI Scan: [NRS (P-f Pre-scan)] | Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and post-dose pre-scan after stimulus |
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| Secondary | Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation After the fMRI Scan: [NRS (T-f Post-scan)] | Subjective NRS response for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on tibio-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and post-dose post-scan after stimulus |
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| Secondary | Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)] | Subjective NRS response for each participant for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine". | ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and post-dose post-scan after stimulus |
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Adverse Events were collected from the time of start of the investigational product, and until 5 days following last administration of the investigational product.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Paracetamol 665 mg | Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water. | 0 | 29 | 3 | 29 | ||
| EG001 | Placebo | Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water. | 0 | 28 | 3 | 28 | ||
| EG002 | No Treatment | No treatment was given to participants. | 0 | 30 | 2 | 30 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Claustrophobia | Psychiatric disorders | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | Systematic Assessment |
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| Bone Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| D010146 | Pain |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000082 | Acetaminophen |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
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| OG002 | No Treatment | No treatment was given to participants. |
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