Trial Outcomes & Findings for A Study of LY2828360 in Patients With Osteoarthritic Knee Pain (NCT NCT01319929)

NCT ID: NCT01319929

Last Updated: 2020-05-19

Results Overview

The weekly mean of the 24-Hour APS was calculated from participants' daily entries for 24-hour average pain rating on an 11-point scale with scores from 0 (no pain) to 10 (worst possible pain). Data were recorded twice a day at approximately the same time each day, preferably first thing in the morning and in the afternoon.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 39 participants
• Primary outcome timeframe: Baseline, 4 weeks
• Results posted on: 2020-05-19

Participant Flow

Participant milestones

Measure	80 mg LY2828360 First, Then Placebo Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks, followed by a 3-week washout period, then placebo once daily by mouth for 4 weeks.	Placebo First, Then 80 mg LY2828360 Participants received placebo once daily by mouth for 4 weeks, followed by a 3-week washout period, then 80 mg of LY2828360 once daily by mouth for 4 weeks.
First Treatment Period (4 Weeks) STARTED	20	19
First Treatment Period (4 Weeks) COMPLETED	17	17
First Treatment Period (4 Weeks) NOT COMPLETED	3	2
Washout Period (3 Weeks) STARTED	17	17
Washout Period (3 Weeks) COMPLETED	17	17
Washout Period (3 Weeks) NOT COMPLETED	0	0
Second Treatment Period (4 Weeks) STARTED	17	17
Second Treatment Period (4 Weeks) COMPLETED	16	16
Second Treatment Period (4 Weeks) NOT COMPLETED	1	1

Reasons for withdrawal

Measure	80 mg LY2828360 First, Then Placebo Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks, followed by a 3-week washout period, then placebo once daily by mouth for 4 weeks.	Placebo First, Then 80 mg LY2828360 Participants received placebo once daily by mouth for 4 weeks, followed by a 3-week washout period, then 80 mg of LY2828360 once daily by mouth for 4 weeks.
First Treatment Period (4 Weeks) Adverse Event	2	0
First Treatment Period (4 Weeks) Withdrawal by Subject	1	1
First Treatment Period (4 Weeks) Protocol Violation	0	1
Second Treatment Period (4 Weeks) Adverse Event	1	0
Second Treatment Period (4 Weeks) Sponsor Decision	0	1

Baseline Characteristics

A Study of LY2828360 in Patients With Osteoarthritic Knee Pain

Baseline characteristics by cohort

Measure	80 mg LY2828360 First, Then Placebo n=20 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks, followed by a 3-week washout period, then placebo once daily by mouth for 4 weeks.	Placebo First, Then 80 mg LY2828360 n=19 Participants Participants received placebo once daily by mouth for 4 weeks, followed by a 3-week washout period, then 80 mg of LY2828360 once daily by mouth for 4 weeks.	Total n=39 Participants Total of all reporting groups
Age, Continuous	64.7 years STANDARD_DEVIATION 6.6 • n=93 Participants	61.9 years STANDARD_DEVIATION 7.1 • n=4 Participants	63.3 years STANDARD_DEVIATION 6.9 • n=27 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	9 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	10 Participants n=4 Participants	25 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants	19 Participants n=4 Participants	39 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment Denmark	20 Participants n=93 Participants	19 Participants n=4 Participants	39 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline and at least 1 post-baseline weekly mean 24-Hour Average Pain value.

The weekly mean of the 24-Hour APS was calculated from participants' daily entries for 24-hour average pain rating on an 11-point scale with scores from 0 (no pain) to 10 (worst possible pain). Data were recorded twice a day at approximately the same time each day, preferably first thing in the morning and in the afternoon.

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Weekly Mean of Daily 24-Hour Average Pain Scores (APS)	-0.90 units on a scale Standard Deviation 1.03	-1.20 units on a scale Standard Deviation 1.50

SECONDARY outcome

Timeframe: Pre-last dose to 8 hours post-last dose (at end of each 4-week treatment period)

Population: The analysis included all randomized participants receiving at least 1 dose of LY2828360 with interpretable PK data.

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo Participants received placebo once daily by mouth for 4 weeks.
Pharmacokinetics (PK) of LY2828360: Maximal Concentration (Cmax)	464.4 nanogram per milliliter (ng/mL) Standard Deviation 161.0	—

SECONDARY outcome

Timeframe: Pre-last dose to 8 hours post-last dose (at end of each 4-week treatment period)

Population: The analysis included all randomized participants receiving at least 1 dose of LY2828360 with interpretable PK data.

AUC from time zero to 8 hours (AUC0-8h) is reported for this outcome measure.

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo Participants received placebo once daily by mouth for 4 weeks.
Pharmacokinetics (PK) of LY2828360: Area Under the Concentration-Time Curve (AUC)	2803.9 nanogram*hour per milliliter (ng*h/mL) Standard Deviation 775.8	—

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline night/worst pain value and at least 1 post-baseline weekly mean night/worst pain value.

The pain severity for night pain and worst pain was measured by an 11-point Likert scale, an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was used for assessment of night pain and worst pain each day, and evaluated as weekly means. Participants were asked to complete the severity pain for worst pain twice a day (in the morning and in the afternoon). The pain severity for night pain was filled out only once in the morning.

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Weekly Mean of Night Pain and Worst Daily Pain Scores Night Pain	-0.80 units on a scale Standard Deviation 1.08	-1.15 units on a scale Standard Deviation 1.47
Change From Baseline to 4 Week Endpoint in Weekly Mean of Night Pain and Worst Daily Pain Scores Worst Daily Pain	-0.85 units on a scale Standard Deviation 1.27	-1.25 units on a scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline and at least 1 postbaseline CPSI value.

The CPSI is a validated 5-item questionnaire in which the following factors were assessed: trouble falling asleep due to pain (CPSI1), the need for sleep medication (CPSI2), awakenings by pain during the night (CPSI3) awakenings by pain in the morning (CPSI4), and overall sleep quality (CSPI5). All CPSI items are scored using a 100-millimeter (mm) visual analog scale (VAS) (VAS; 0=never and 100=always for CPSI1 through CPSI4, and 0=very poor and 100=excellent for CPSI5).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI) CPSI1: Trouble falling asleep due to pain	-0.6 units on a scale Standard Deviation 0.9	-0.6 units on a scale Standard Deviation 1.2
Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI) CPSI2: Need for sleep medication	0.0 units on a scale Standard Deviation 0.3	-0.1 units on a scale Standard Deviation 0.5
Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI) CPSI3: Awakenings by pain during the night	-0.5 units on a scale Standard Deviation 1.2	-0.8 units on a scale Standard Deviation 1.5
Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI) CPSI4: Awakenings by pain in the morning	-0.4 units on a scale Standard Deviation 1.1	-0.7 units on a scale Standard Deviation 1.2
Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI) CPSI5: Overall sleep quality	0.8 units on a scale Standard Deviation 1.4	1.3 units on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline and at least 1 postbaseline PSQI value.

The PSQI is a self-rated questionnaire that assesses the participant's sleep habits during the last month and consists of 19 questions that cover 7 components (sleep quality, sleep onset latency, sleep duration, sleep efficiency, sleep disturbances, sleeping medication use, and daytime dysfunction). Each item has a range of 0 (no difficulty) to 3 (severe difficulty). The 7 component scores were added to yield a global score with a range of 0 (no difficulty) to 21 (severe difficulties in all areas).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Pittsburgh Sleep Quality Index (PSQI)	-0.9 units on a scale Standard Deviation 2.8	-0.7 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with baseline and at least 1 postbaseline BPI-S/BPI-I value.

The BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. BPI-S consists of 4 questions assessing worst pain, least pain, average pain in the past 24 hours, and pain right now. Severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The BPI-I average interference is the average of 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference scores range: 0 (does not interfere) to 10 (completely interferes).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) BPI-S Worst Pain	-1.0 units on a scale Standard Deviation 1.7	-1.0 units on a scale Standard Deviation 1.9
Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) BPI-S Least Pain	-0.6 units on a scale Standard Deviation 1.0	-0.8 units on a scale Standard Deviation 1.8
Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) BPI-S Average Pain in the Past 24 Hours	-0.9 units on a scale Standard Deviation 1.1	-1.1 units on a scale Standard Deviation 1.6
Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) BPI-S Pain Right Now	-0.6 units on a scale Standard Deviation 1.4	-0.8 units on a scale Standard Deviation 1.7
Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) BPI-I Average Interference	-0.7 units on a scale Standard Deviation 1.2	-0.8 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with baseline and at least 1 postbaseline IGAC value.

The IGAC is an investigator-reported subjective evaluation using a 100 millimeter (mm) visual analog scale (VAS) to answer the following question: If you take into consideration all the various ways the knee pain influence the participant and his/her life, how do you then evaluate the participant's condition today (0=very good and 100=very bad).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Investigator Global Assessment of Changes (IGAC)	-8.6 units on a scale Standard Deviation 15.6	-8.6 units on a scale Standard Deviation 16.2

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants who received at least 1 dose of the investigational product and with a baseline and at least 1 postbaseline PGAC value.

The PGAC is a self-reported subjective evaluation using a 100 millimeter (mm) visual analog scale (VAS) to answer the following question: If you take into consideration all the various ways the knee pain influence you and your life how do you then evaluate your condition over the last week (0=very good and 100=very bad).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Patient Global Assessment of Changes (PGAC)	-9.6 units on a scale Standard Deviation 21.7	-10.5 units on a scale Standard Deviation 21.3

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline and at least 1 postbaseline WOMAC value.

WOMAC index completed by participant; consists of 24 questions, each based on 5-point Likert scale (0=none to 4=extreme). Has 3 subscales: pain, stiffness, and physical function. Pain subscale has 5 questions on pain associated with everyday tasks; subscale score ranges from 0=none to 20=extreme. Physical function subscale has 17 questions on physical function difficulties with everyday tasks; subscale score ranges from 0=none to 68=extreme. Stiffness subscale has 2 questions on stiffness associated with time of day (morning versus later in day); subscale score ranges from 0=none to 8=extreme.

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Western Ontario and MacMaster (WOMAC) WOMAC: Pain	-0.9 units on a scale Standard Deviation 2.3	-1.6 units on a scale Standard Deviation 2.5
Change From Baseline to 4 Week Endpoint in Western Ontario and MacMaster (WOMAC) WOMAC: Stiffness	-0.5 units on a scale Standard Deviation 1.4	-0.5 units on a scale Standard Deviation 1.5
Change From Baseline to 4 Week Endpoint in Western Ontario and MacMaster (WOMAC) WOMAC: Physical Function	-3.4 units on a scale Standard Deviation 7.8	-3.9 units on a scale Standard Deviation 7.9

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of the investigational product and with a baseline and at least 1 postbaseline 40 Meter Self-Paced Walk test value.

The 40 meter self-paced walk test is a participant-rated subjective evaluation using a 100 millimeter (mm) visual analog scale (VAS) to assess pain after walking 40 meters. Scores range from 0 (no pain) to 100 (worst pain).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in Pain From 40 Meter Self-Paced Walk Test	-7.8 units on a scale Standard Deviation 18.0	-8.4 units on a scale Standard Deviation 24.7

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of investigational product and with baseline and at least 1 postbaseline 11 Step Stair Climb Test value.

The 11 step stair climb test is a participant-rated subjective evaluation using a 100 millimeter (mm) visual analog scale (VAS) to assess pain after climbing 11 stairs. Scores range from 0 (no pain) to 100 (worst pain).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in the 11 Step Stair Climb Test	-4.0 units on a scale Standard Deviation 16.0	-9.0 units on a scale Standard Deviation 23.9

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: The analysis included all randomized participants receiving at least 1 dose of investigational product and with a baseline and at least 1 postbaseline DoloTest value.

The DoloTest® is a self-reported assessment composed of 8 visual analog scale (VAS) items ranging from 0 (none) to 100 (worst possible) for the following domains: pain, problems with light physical activities, problems with more strenuous physical activities, problems doing your job, reduced energy and strength, low spirit, reduced social life, and problems sleeping). The scale is arranged in a radar plot to provide a graphic presentation of the test result. The DoloTest® Sum Score is equal to the sum of each scored domain; scores range from 0 (none) to 800 (worst possible).

Outcome measures

Measure	80 mg LY2828360 n=34 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=34 Participants Participants received placebo once daily by mouth for 4 weeks.
Change From Baseline to 4 Week Endpoint in DoloTest Sum Score	-34.5 units on a scale Standard Deviation 90.0	-51.5 units on a scale Standard Deviation 88.6

SECONDARY outcome

Timeframe: Baseline up to 15 weeks

Population: The C-SSRS analysis included all randomized participants.

C-SSRS: scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors and ideations are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation.

Outcome measures

Measure	80 mg LY2828360 n=37 Participants Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=36 Participants Participants received placebo once daily by mouth for 4 weeks.
Number of Participants With Treatment-Emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Ideation	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Behaviors	0 Participants	0 Participants

Adverse Events

80 mg LY2828360

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	80 mg LY2828360 n=37 participants at risk Participants received 80 milligrams (mg) of LY2828360 once daily by mouth for 4 weeks.	Placebo n=36 participants at risk Participants received placebo once daily by mouth for 4 weeks.
Gastrointestinal disorders Diarrhoea	2.7% 1/37 • Number of events 1	5.6% 2/36 • Number of events 3
Gastrointestinal disorders Nausea	10.8% 4/37 • Number of events 5	2.8% 1/36 • Number of events 1
Gastrointestinal disorders Toothache	2.7% 1/37 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Vomiting	0.00% 0/37	2.8% 1/36 • Number of events 2
General disorders Fatigue	5.4% 2/37 • Number of events 2	2.8% 1/36 • Number of events 1
General disorders Oedema peripheral	2.7% 1/37 • Number of events 1	0.00% 0/36
Infections and infestations Cystitis	2.7% 1/37 • Number of events 1	5.6% 2/36 • Number of events 2
Infections and infestations Nasopharyngitis	2.7% 1/37 • Number of events 1	5.6% 2/36 • Number of events 3
Infections and infestations Otitis externa	0.00% 0/37	2.8% 1/36 • Number of events 1
Infections and infestations Tooth infection	2.7% 1/37 • Number of events 1	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 1/37 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/37	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Joint swelling	2.7% 1/37 • Number of events 1	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle spasms	2.7% 1/37 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	2.7% 1/37 • Number of events 2	0.00% 0/36
Musculoskeletal and connective tissue disorders Osteoarthritis	2.7% 1/37 • Number of events 1	8.3% 3/36 • Number of events 3
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/37	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/37	2.8% 1/36 • Number of events 1
Nervous system disorders Dizziness	10.8% 4/37 • Number of events 5	2.8% 1/36 • Number of events 1
Nervous system disorders Headache	10.8% 4/37 • Number of events 5	5.6% 2/36 • Number of events 2
Nervous system disorders Sciatica	0.00% 0/37	2.8% 1/36 • Number of events 1
Psychiatric disorders Insomnia	0.00% 0/37	2.8% 1/36 • Number of events 1
Skin and subcutaneous tissue disorders Rash	2.7% 1/37 • Number of events 2	0.00% 0/36

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60