Trial Outcomes & Findings for Chronic Pain Master Protocol (CPMP): A Study of LY3556050 in Participants With Osteoarthritis (NCT NCT04627038)

Last Updated: 2023-11-02

Results Overview

The NRS was used to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95 percent (%) credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

202 participants

Primary outcome timeframe

Baseline, Week 8

Results posted on

2023-11-02

Participant Flow

Participant milestones

Participant milestones
Measure	LY3556050 600 Milligram (mg) Participants received 600 mg LY3556050 twice daily (BID) every 12 hours for up to 8 weeks.	Placebo Participants received placebo BID every 12 hours for up to 8 weeks.
Overall Study STARTED	135	67
Overall Study Received at Least One Dose of Study Drug	135	66
Overall Study COMPLETED	81	53
Overall Study NOT COMPLETED	54	14

Reasons for withdrawal

Reasons for withdrawal
Measure	LY3556050 600 Milligram (mg) Participants received 600 mg LY3556050 twice daily (BID) every 12 hours for up to 8 weeks.	Placebo Participants received placebo BID every 12 hours for up to 8 weeks.
Overall Study Adverse Event	36	8
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1
Overall Study Protocol Violation	3	1
Overall Study Withdrawal by Subject	13	3
Overall Study Non-compliance with study drug	0	1
Overall Study Prohibited Concomitant Medication	1	0

Baseline Characteristics

Chronic Pain Master Protocol (CPMP): A Study of LY3556050 in Participants With Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY3556050 600 mg n=135 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=67 Participants Participants received placebo BID every 12 hours for up to 8 weeks.	Total n=202 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	76 Participants n=5 Participants	33 Participants n=7 Participants	109 Participants n=5 Participants
Age, Categorical >=65 years	59 Participants n=5 Participants	34 Participants n=7 Participants	93 Participants n=5 Participants
Age, Continuous	62.8 years STANDARD_DEVIATION 8.4 • n=5 Participants	62.8 years STANDARD_DEVIATION 8.8 • n=7 Participants	62.8 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	39 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	28 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	10 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	108 Participants n=5 Participants	57 Participants n=7 Participants	165 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	13 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) White	106 Participants n=5 Participants	51 Participants n=7 Participants	157 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	135 Participants n=5 Participants	67 Participants n=7 Participants	202 Participants n=5 Participants
Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)	5.58 score on a scale STANDARD_DEVIATION 1.68 • n=5 Participants	5.54 score on a scale STANDARD_DEVIATION 1.57 • n=7 Participants	5.57 score on a scale STANDARD_DEVIATION 1.64 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: All enrolled participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=63 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=46 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)	-1.67 score on a scale Interval -2.05 to -1.3	-1.76 score on a scale Interval -2.23 to -1.29

SECONDARY outcome

Timeframe: Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the 5 questions for each participant at each time point. The range of possible scores is 0 to 20 with higher scores representing worse outcome. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the Western Ontario and McMaster University Arthritis Index (WOMAC®) Pain Subscale	-2.57 score on a scale Interval -3.22 to -1.9	-3.51 score on a scale Interval -4.35 to -2.67

SECONDARY outcome

Timeframe: Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for the stiffness subscale was calculated by summing the scores of the 2 questions for each participant at each time point. The range of possible scores is 0 to 8 with higher scores representing worse outcome. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the WOMAC® Stiffness Subscale	-1.15 score on a scale Interval -1.48 to -0.81	-1.39 score on a scale Interval -1.79 to -0.99

SECONDARY outcome

Timeframe: Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no difficulty, and 4 = extreme difficulty. The score for physical function subscale was calculated by summing the scores of the 17 questions for each participant at each time point. The range of possible scores is 0 to 68 with higher scores representing worse outcome. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the WOMAC® Physical Function Subscale	-8.33 score on a scale Interval -10.45 to -6.17	-12.18 score on a scale Interval -14.92 to -9.39

SECONDARY outcome

Timeframe: Baseline, Week 8

Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change	2.76 score on a scale Interval 2.53 to 3.0	2.86 score on a scale Interval 2.57 to 3.16

SECONDARY outcome

Timeframe: Baseline, Week 8

The NRS was used to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=63 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=46 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline for Worst Pain Intensity as Measured by NRS	-1.74 score on a scale Interval -2.14 to -1.33	-2.05 score on a scale Interval -2.55 to -1.54

SECONDARY outcome

Timeframe: Baseline, Week 8

VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the Visual Analog Scale (VAS) for Pain	-19.69 score on a scale Interval -24.36 to -15.05	-25.93 score on a scale Interval -31.84 to -19.93

SECONDARY outcome

Timeframe: Baseline, Week 8

The MOS Sleep Scale consists of 12 questions addressing the past week. Question 1 asks time to fall asleep and it is reported in 5-point timeframe categories. Question 2 asks average hours of sleep. In the remaining 10 questions participants report how often a sleep symptom or problem was present on a scale ranging from '0=all of the time' to '5=none of the time.' MOS Sleep scale dimension scores range from 0 to 100 with lower score indicating improvement, except for the dimension of sleep adequacy, where higher scores indicate improvement. Here, the average hours of sleep (i.e., Question 2) is reported as the average number of hours slept each night during the past week (range 0 to 24 hours). Higher number of hours slept indicates improvement. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=52 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep	0.15 Hours per night Interval -0.05 to 0.34	-0.01 Hours per night Interval -0.25 to 0.23

SECONDARY outcome

Timeframe: Week 8

Total amount of rescue medication use as measured by average daily dosage. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=63 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=46 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Total Amount of Rescue Medication Use as Measured by Average Daily Dosage	247.24 mg per day (mg/day) Interval 146.1 to 349.69	248.06 mg per day (mg/day) Interval 115.23 to 380.78

SECONDARY outcome

Timeframe: Baseline, Week 8

The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score using the United States algorithm. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0=a health state equivalent to death, and 1=perfect health. Posterior mean change from baseline, 95% credible intervals was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Outcome measures

Outcome measures
Measure	LY3556050 600 mg n=81 Participants Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=53 Participants Participants received placebo BID every 12 hours for up to 8 weeks.
Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) Questionnaire (EQ-5D-5L) Health State Index (United States Algorithm)	0.03 score on a scale Interval -0.02 to 0.09	0.05 score on a scale Interval -0.01 to 0.11

Adverse Events

LY3556050 600 mg

Serious events: 0 serious events

Other events: 83 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LY3556050 600 mg n=135 participants at risk Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=66 participants at risk Participants received placebo BID every 12 hours for up to 8 weeks.
Infections and infestations Covid-19 pneumonia	0.00% 0/135 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/135 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	LY3556050 600 mg n=135 participants at risk Participants received 600 mg LY3556050 BID every 12 hours for up to 8 weeks.	Placebo n=66 participants at risk Participants received placebo BID every 12 hours for up to 8 weeks.
Gastrointestinal disorders Abdominal discomfort	5.2% 7/135 • Number of events 8 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	5.9% 8/135 • Number of events 8 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	21.5% 29/135 • Number of events 31 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	4.5% 3/66 • Number of events 3 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	9.6% 13/135 • Number of events 13 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	4.4% 6/135 • Number of events 6 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	19.3% 26/135 • Number of events 29 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	9.1% 6/66 • Number of events 8 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
General disorders Fatigue	14.1% 19/135 • Number of events 21 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 1 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 6/135 • Number of events 6 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	6.1% 4/66 • Number of events 9 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Nervous system disorders Dizziness	16.3% 22/135 • Number of events 25 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	1.5% 1/66 • Number of events 2 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Nervous system disorders Headache	5.9% 8/135 • Number of events 8 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	10.6% 7/66 • Number of events 12 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.
Nervous system disorders Lethargy	5.2% 7/135 • Number of events 7 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.	0.00% 0/66 • Baseline through Week 8 All enrolled participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place