Trial Outcomes & Findings for Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel (NCT NCT01637077)

Results Overview

Worst of the pain scores for the week following the first cycle of paclitaxel administration, as measured by a question on the daily post-paclitaxel questionnaire. Worst pain over the first 6 days following treatment initiation. Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

From treatment initiation to 6 days following treatment initiation; up to 7 days

Results posted on

2018-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Pregabalin) Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Overall Study STARTED	23	23
Overall Study COMPLETED	19	22
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Pregabalin) Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Overall Study Cancel	1	1
Overall Study Withdrawal by Subject	1	0
Overall Study No cycle 1 questionnaire data	2	0

Baseline Characteristics

Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Total n=41 Participants Total of all reporting groups
Age, Continuous	54.2 years STANDARD_DEVIATION 12.9 • n=5 Participants	53.2 years STANDARD_DEVIATION 14.3 • n=7 Participants	53.7 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

Worst of the pain scores for the week following the first cycle of paclitaxel administration, as measured by a question on the daily post-paclitaxel questionnaire. Worst pain over the first 6 days following treatment initiation. Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score	2.6 units on a scale Standard Deviation 2.5	3.2 units on a scale Standard Deviation 3.0

PRIMARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

Maximum of average pain scores over 6 days following initiation of treatment. Average pain over the first 6 days following treatment initiation. Maximum of the average pain scores (item 3, appendix IV; "Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in the last 24 hours.") over the period from treatment initiation to day 7 (for cycle 1). Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1).	2.6 units on a scale Standard Deviation 2.2	2.2 units on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

Population: The number analyzed for average pain over the past 24 hours differs from the overall number analyzed due to missing data.

Average Area Under the Curve per assessment (aAUCpa) of worst, average, and least pain (items 1-3 app. IV; "Please rate any aches/pains that are NEW since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment by circling ONE number that best describes your aches/pains at its WORST in the last 24 hours.", "Please rate the same aches/pains by circling the ONE number that best describes your aches/pains at its LEAST in the last 24 hours.", "Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in the last 24 hours.") for the first cycle of treatment. Scores are reported on a 0-100 scale, where 100=better outcome QOL. The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the day-6 assessment.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. Worst pain over the past 24 hours	80.7 average(subscale value*assessment) Standard Deviation 22.3	82.6 average(subscale value*assessment) Standard Deviation 24.0
Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. Average pain over the past 24 hours	82.8 average(subscale value*assessment) Standard Deviation 20.2	86.8 average(subscale value*assessment) Standard Deviation 19.7
Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. Least pain over the past 24 hours	82.6 average(subscale value*assessment) Standard Deviation 23.0	91.3 average(subscale value*assessment) Standard Deviation 14.8

SECONDARY outcome

Timeframe: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment	2.2 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 months.

The percentage of patients who use non-prescription pain medications are reported by arm below.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Percentage of Patients Who Use Non-prescription Pain Medications	52.6 percentage of patients	50 percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 months.

The percentage of patients taking opioid medications are reported below by arm.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Percentage of Patients Taking Opioid Medications	15.8 percentage of patients	18.2 percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

The percentage of patients who report the development of new aches/pains that they attribute to paclitaxel in the first week of chemotherapy are reported by arm below.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel	23.5 percentage of patients	59.1 percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

The worst pain reported at the end of the week for the overall week ("New aches and pains at their worst over the past week") are reported below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not. The worst pain reported at the end of the week for the overall week (item 2 appendix V: "Please rate any aches/pains that you have by circling ONE number that best describes your aches/pains at its worst over the last week.") Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V)	2.4 units on a scale Standard Deviation 2.1	4.7 units on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

The percentage of patients who report, at week's end, using non-prescription pain medications ("Have you used non-prescription meds like aspirin, Tylenol, Motrin, Ibuprofen, or Advil over the past week?") are reported by arm below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications	66.7 percentage of patients	60. percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 days following treatment initiation; up to 7 days

The percentage of patients who report, at week's end, using opioids ("Have you used opioids like codeine, oxycodone, or morphine for this pain over the past week?") are reported by arm below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
The Percentage of Patients Who Report, at Week's End, Using Opioids	0 percentage of patients	26.7 percentage of patients

SECONDARY outcome

Timeframe: From treatment initiation to 6 months.

Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neurophathy Module (EORTC QLQ-CIPN20) Sensory, Autonomic, and Motor Neuropathy Subscales. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48), motor (items 37, 38, 41-45, 49), and autonomic (items 46, 47, 50) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the 6-month assessment. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to 6-months are averaged to yield the aAUCpa per patient per subcale.

Outcome measures

Outcome measures
Measure	Arm I (Pregabalin) n=19 Participants Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 Participants Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales Sensory	88.4 average(subscale value*assessment) Standard Deviation 12.5	84.5 average(subscale value*assessment) Standard Deviation 16.7
Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales Autonomic	88.4 average(subscale value*assessment) Standard Deviation 17.6	88.6 average(subscale value*assessment) Standard Deviation 15.8
Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales Motor	92.0 average(subscale value*assessment) Standard Deviation 11.0	90.2 average(subscale value*assessment) Standard Deviation 10.7

Adverse Events

Arm I (Pregabalin)

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Pregabalin) n=21 participants at risk Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Arm II (Placebo) n=22 participants at risk Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Gastrointestinal disorders Constipation	0.00% 0/21 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.	4.5% 1/22 • Number of events 1 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.
Metabolism and nutrition disorders Hyponatremia	4.8% 1/21 • Number of events 1 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.	0.00% 0/22 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.
Nervous system disorders Cognitive disturbance	4.8% 1/21 • Number of events 2 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.	0.00% 0/22 • Time Frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment The revised NCI Common Terminology Criteria for AE (CTCAE) version 4.0 will be utilized for AE reporting. Cancels and Withdrawal by Subject in the Participant Flow table did not receive treatment. Serious AE (SAE) reports for this study may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited Adverse Events (EAEs), and appear in the SAE table.

Other adverse events

Additional Information

Charles L. Loprinzi, M.D.

Mayo Clinic

Phone: 507/284-1623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place