Trial Outcomes & Findings for Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain (NCT NCT01912612)

NCT ID: NCT01912612

Last Updated: 2020-08-06

Results Overview

Worst pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory. * Baseline: Mean worst pain for all individual patients in arm 1 (intervention) and arm 2 (control) * 5 weeks: Mean worst pain for all individual patients in arm 1 (intervention) * Range of pain score 0-10 (0=no pain; 10=worst pain)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 82 participants
• Primary outcome timeframe: 5 weeks
• Results posted on: 2020-08-06

Participant Flow

3 cases randomized to placebo are not included in the analysis. See study description in protocol section for explanation. 3 patients on Arm 2 consented but withdrew prior to participation. 1 patient on Arm 1 withdrew permission to use her data.

Participant milestones

Measure	Arm 1 (Patients With Pain) Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days. Surveys administered at baseline and at 5 weeks.	Arm 2 (Patients Without Pain -- Control) Surveys administered at baseline only.	Arm 3 - Placebo (Withdrawn) Because of challenges with logistics of the protocol and pain testing, the trial was redesigned after only 7 patients with pain were enrolled. Three of the patients had been assigned to placebo arm. This arm is not included in any analysis.
Overall Study STARTED	36	40	3
Overall Study COMPLETED	31	40	0
Overall Study NOT COMPLETED	5	0	3

Reasons for withdrawal

Measure	Arm 1 (Patients With Pain) Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days. Surveys administered at baseline and at 5 weeks.	Arm 2 (Patients Without Pain -- Control) Surveys administered at baseline only.	Arm 3 - Placebo (Withdrawn) Because of challenges with logistics of the protocol and pain testing, the trial was redesigned after only 7 patients with pain were enrolled. Three of the patients had been assigned to placebo arm. This arm is not included in any analysis.
Overall Study Adverse Event	4	0	0
Overall Study Withdrew consent	1	0	0
Overall Study Study design change	0	0	3

Baseline Characteristics

Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain

Baseline characteristics by cohort

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.	Total n=75 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	54 years n=7 Participants	55 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	40 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	40 Participants n=7 Participants	75 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	37 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	40 participants n=7 Participants	78 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Worst pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.

• Baseline: Mean worst pain for all individual patients in arm 1 (intervention) and arm 2 (control)
• 5 weeks: Mean worst pain for all individual patients in arm 1 (intervention)
• Range of pain score 0-10 (0=no pain; 10=worst pain)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Patient-reported Worst Pain Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	6.54 score on a scale Standard Deviation 1.868	0.25 score on a scale Standard Deviation 0.494
Change in Patient-reported Worst Pain Between Baseline and 5 Weeks of Treatment With Duloxetine 5 weeks	4.06 score on a scale Standard Deviation 2.744	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Average pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.

• Baseline: Mean average pain for all individual patients in arm 1 (intervention) and arm 2 (control)
• 5 weeks: Mean average pain for all individual patients in arm 1 (intervention)
• Range of pain score 0-10 (0=no pain; 10=worst pain)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Patient-reported Average Pain Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	4.86 score on a scale Standard Deviation 2.088	0.15 score on a scale Standard Deviation 0.362
Change in Patient-reported Average Pain Between Baseline and 5 Weeks of Treatment With Duloxetine 5 week timepoint	3.10 score on a scale Standard Deviation 2.271	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 had missing data at baseline and the score could not be generated.

Pain interference will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory.

• Baseline: Mean pain interference for all individual patients in arm 1 (intervention)
• 5 weeks: Mean pain interference for all individual patients in arm 1 (intervention)
• Range of pain interference score 0-10 (0=no interference; 10=worst interference)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Pain Interference Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	4.91 score on a scale Standard Deviation 2.09	0.03 score on a scale Standard Deviation 0.74
Change in Pain Interference Between Baseline and 5 Weeks of Treatment With Duloxetine 5 week timepoint	2.30 score on a scale Standard Deviation 2.33	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Number of sites of pain will be assessed at baseline and 5 weeks for each individual patient using the Michigan Body Map.

• Baseline: Mean number of sites of pain for all individual patients in arm 1 (intervention)
• 5 weeks: Mean number of sites of pain for all individual patients in arm 1 (intervention)
• Range of number of sites of pain 0-35 (0=no pain; 35=every pre-defined body site has pain)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Number of Sites of Pain Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	9.63 number of sites Interval 1.0 to 22.0	0.52 number of sites Interval 0.0 to 4.0
Change in Number of Sites of Pain Between Baseline and 5 Weeks of Treatment With Duloxetine 5 week timepoint	7.90 number of sites Interval 1.0 to 18.0	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 had missing data at baseline and the score could not be generated.

Fibromyalgia Symptom Severity Score will be assessed at baseline and 5 weeks for each individual patient using the Michigan Body Map and Symptom Severity Scale.

• Baseline: Mean Fibromyalgia Symptom Severity Score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean Fibromyalgia Symptom Severity Score for all individual patients in arm 1 (intervention)
• Range of Fibromyalgia Symptom Severity Score 0-12 (0=not consistent with fibromyalgia; 12=most consistent with fibromyalgia)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Fibromyalgia Symptom Severity Score Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	5.35 score on a scale Standard Deviation 2.13	1.68 score on a scale Standard Deviation 1.37
Change in Fibromyalgia Symptom Severity Score Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	4.90 score on a scale Standard Deviation 2.44	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 had missing data at baseline and 3 patients had missing data at week 5 and the scores could not be generated.

PainDETECT score will be assessed at baseline and 5 weeks for each individual patient using the PainDETECT questionnaire.

• Baseline: Mean PainDETECT score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean PainDETECT score for all individual patients in arm 1 (intervention)
• Range of PainDETECT score -1-38 (-1=no neuropathic pain; 38=most consistent with neuropathic pain)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in PainDETECT Score Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	11.44 score on questionnaire Standard Deviation 8.39	1.13 score on questionnaire Standard Deviation 2.02
Change in PainDETECT Score Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	8.54 score on questionnaire Standard Deviation 8.72	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline, 1 patient in Arm 1 at week 5, and 1 patient in Arm 2 had missing data and the scores could not be generated.

Neuropathy will be assessed at baseline and 5 weeks for each individual patient using the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) questionnaire.

• Baseline: Mean neuropathy score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean neuropathy score for all individual patients in arm 1 (intervention)
• Range of neuropathy score 0-44 (0=no neuropathy; 44=most consistent with neuropathy)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Neuropathy Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	14.09 score on questionnaire Standard Deviation 8.85	1.44 score on questionnaire Standard Deviation 1.67
Change in Neuropathy Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	9.10 score on questionnaire Standard Deviation 8.77	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Fatigue will be assessed at baseline and 5 weeks for each individual patient using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.

• Baseline: Mean fatigue T score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean fatigue T score for all individual patients in arm 1 (intervention)
• Average fatigue T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=more fatigue)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Fatigue Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	56.79 T score Standard Deviation 7.86	45.63 T score Standard Deviation 5.53
Change in Fatigue Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	54.51 T score Standard Deviation 7.84	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Sleep Disturbance will be assessed at baseline and 5 weeks for each individual patient using the PROMIS Sleep Disturbance Short Form 8b v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.

• Baseline: Mean sleep disturbance T score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean sleep disturbance T score for all individual patients in arm 1 (intervention)
• Average sleep disturbance T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=more sleep disturbance)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Sleep Disturbance Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	57.44 T score Standard Deviation 8.25	43.91 T score Standard Deviation 7.99
Change in Sleep Disturbance Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	53.85 T score Standard Deviation 8.86	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5.

Physical Function will be assessed at baseline and 5 weeks for each individual patient using the PROMIS Physical Function Short Form 10a v1.0 questionnaire. Raw scores are converted to standardized T scores based on national norms for patients with cancer.

• Baseline: Mean physical function T score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean physical function T score for all individual patients in arm 1 (intervention)
• Average physical function T score for the reference population of patients with cancer is 50.0, with standard deviation of 10.0 (higher score=better physical function)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Physical Function Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	41.96 T score Standard Deviation 5.58	56.60 T score Standard Deviation 5.74
Change in Physical Function Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	44.03 T score Standard Deviation 6.13	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 had missing data at baseline and the score could not be generated.

Anxiety will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale.

• Baseline: Mean anxiety score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean anxiety score for all individual patients in arm 1 (intervention)
• Range of anxiety score 0-21 (0=no anxiety, 21=maximum anxiety)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Anxiety Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	6.97 score on a scale Standard Deviation 4.00	3.90 score on a scale Standard Deviation 2.91
Change in Anxiety Between Baseline and 5 Weeks of Treatment With Duloxetine week 4 timepoint	5.03 score on a scale Standard Deviation 3.15	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline and 1 patient in Arm 2 had missing data and the scores could not be generated.

Depression will be assessed at baseline and 5 weeks for each individual patient using the Hospital Anxiety and Depression Scale.

• Baseline: Mean depression score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean depression score for all individual patients in arm 1 (intervention)
• Range of depression score 0-21 (0=no depression, 21=maximum depression)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Depression Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	5.85 score on a scale Standard Deviation 3.38	1.46 score on a scale Standard Deviation 1.95
Change in Depression Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	4.23 score on a scale Standard Deviation 3.96	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at week 5 had missing data and the score could not be generated.

Cognitive Difficulties - Language will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.

• Baseline: Mean language score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean language score for all individual patients in arm 1 (intervention)
• Range of language score 0-40 (0=no language difficulties, 40=maximum language difficulties)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Cognitive Difficulties - Language Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	15.43 score on a scale Standard Deviation 4.51	12.42 score on a scale Standard Deviation 3.40
Change in Cognitive Difficulties - Language Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	14.83 score on a scale Standard Deviation 3.57	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline, 1 patient in Arm 1 at week 5, and 1 patient in Arm 2 had missing data and the scores could not be generated.

Cognitive Difficulties - Visual-Perceptual Ability will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.

• Baseline: Mean visual-perceptual ability score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean visual-perceptual ability score for all individual patients in arm 1 (intervention)
• Range of visual-perceptual ability score 0-30 (0=no visual-perceptual difficulties, 30=maximum visual-perceptual difficulties)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Cognitive Difficulties - Visual-Perceptual Ability Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	10.79 score on a scale Standard Deviation 3.17	8.62 score on a scale Standard Deviation 3.39
Change in Cognitive Difficulties - Visual-Perceptual Ability Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	10.33 score on a scale Standard Deviation 2.70	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline, 1 patient in arm 1 at week 5, and 1 patient in Arm 2 had missing data and the scores could not be generated.

Cognitive Difficulties - Verbal Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.

• Baseline: Mean verbal memory score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean verbal memory score for all individual patients in arm 1 (intervention)
• Range of verbal memory score 0-40 (0=no verbal memory difficulties, 40=maximum verbal memory difficulties)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Cognitive Difficulties - Verbal Memory Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	17.15 score on a scale Standard Deviation 4.57	13.97 score on a scale Standard Deviation 4.36
Change in Cognitive Difficulties - Verbal Memory Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	16.90 score on a scale Standard Deviation 3.83	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at week 5 and 1 patient in Arm 2 had missing data and the scores could not be generated.

Cognitive Difficulties - Visual-Spatial Memory will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.

• Baseline: Mean visual-spatial memory score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean visual-spatial memory score for all individual patients in arm 1 (intervention)
• Range of visual-spatial memory score 0-40 (0=no visual-spatial memory difficulties, 40=maximum visual-spatial memory difficulties)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Cognitive Difficulties - Visual-Spatial Memory Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	14.43 score on a scale Standard Deviation 3.07	13.03 score on a scale Standard Deviation 4.84
Change in Cognitive Difficulties - Visual-Spatial Memory Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	14.53 score on a scale Standard Deviation 3.64	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline, 1 patient in Arm 1 at week 5, and 1 patient in Arm 2 had missing data and the scores could not be generated.

Cognitive Difficulties - Attention/Concentration will be assessed at baseline and 5 weeks for each individual patient using the Multiple Ability Self-Report Questionnaire.

• Baseline: Mean attention/concentration score for all individual patients in arm 1 (intervention)
• 5 weeks: Mean attention/concentration score for all individual patients in arm 1 (intervention)
• Range of attention/concentration score 0-40 (0=no attention/concentration difficulties, 40=maximum attention/concentration difficulties)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=39 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Cognitive Difficulties - Attention/Concentration Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	17.26 score on a scale Standard Deviation 3.43	14.10 score on a scale Standard Deviation 3.60
Change in Cognitive Difficulties - Attention/Concentration Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	15.83 score on a scale Standard Deviation 3.49	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 had missing data at week 5 and the score could not be generated.

Pain sensitivity will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing to assess pressure pain threshold (Pain50).

• Baseline: Mean Pain50 for all individual patients in arm 1 (intervention) and arm 2 (control)
• 5 weeks: Mean Pain50 for all individual patients in arm 1 (intervention)
• Range of Pain50 score: 0-10 kg/cm2 (higher number reflects higher pain threshold or lower pain sensitivity)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=35 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Objectively Assessed Pain Sensitivity Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	3.20 kg/cm2 Standard Deviation 1.37	4.06 kg/cm2 Standard Deviation 1.40
Change in Objectively Assessed Pain Sensitivity Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	3.30 kg/cm2 Standard Deviation 1.38	—

SECONDARY outcome

Timeframe: 5 weeks

Population: Only patients with pain were analyzed at week 5. Patients who discontinued study treatment early (n=4) have no data available for week 5. 1 patient in Arm 1 at baseline, 1 patient in Arm 1 at week 5, and 2 patients in Arm 2 had missing data and the scores could not be generated.

Conditioned pain modulation (CPM) will be assessed at baseline and 5 weeks for each individual patient using quantitative sensory testing

• Baseline: Mean CPM for all individual patients in arm 1 (intervention) and arm 2 (control)
• 5 weeks: Mean CPM for all individual patients in arm 1 (intervention)
• Range of CPM score: -60 to +60 (more positive values reflect more impaired CPM)

Outcome measures

Measure	Arm 1 (Patients With Pain) n=34 Participants Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=38 Participants Patient reported pain and symptoms assessment for comparison at baseline.
Change in Objectively Assessed Conditioned Pain Modulation Between Baseline and 5 Weeks of Treatment With Duloxetine Baseline	9.68 score on a scale Standard Deviation 16.47	7.97 score on a scale Standard Deviation 15.32
Change in Objectively Assessed Conditioned Pain Modulation Between Baseline and 5 Weeks of Treatment With Duloxetine week 5 timepoint	11.93 score on a scale Standard Deviation 12.76	—

Adverse Events

Arm 1 (Patients With Pain)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Arm 2 (Patients Without Pain -- Control)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm 1 (Patients With Pain) n=35 participants at risk Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 participants at risk Patient reported pain and symptoms assessment for comparison at baseline.
Cardiac disorders congestive heart failure	2.9% 1/35 • Number of events 1 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug

Other adverse events

Measure	Arm 1 (Patients With Pain) n=35 participants at risk Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks. Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.	Arm 2 (Patients Without Pain -- Control) n=40 participants at risk Patient reported pain and symptoms assessment for comparison at baseline.
Nervous system disorders Dizziness	11.4% 4/35 • Number of events 4 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug
Nervous system disorders headache	8.6% 3/35 • Number of events 3 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug
Psychiatric disorders insomnia	8.6% 3/35 • Number of events 3 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug
General disorders fatigue	5.7% 2/35 • Number of events 2 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug
Gastrointestinal disorders nausea	11.4% 4/35 • Number of events 4 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug	0.00% 0/40 • Adverse Event (AE) data were collected from date of study drug administration until 14 days after completion of study drug

Additional Information

Lynn Henry, MD, PhD

University of Michigan Rogel Cancer Center

Phone: 734-936-9868

Email: norahh@med.umich.edu

Results disclosure agreements

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