Trial Outcomes & Findings for A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer (NCT NCT00381095)

Last Updated: 2021-01-20

Results Overview

DAAC from baseline based on Numeric Rating Scale (NRS) score for Worst Pain at Reference site from the last day dose adjustment was needed (fixed dosing date) to day 28. DAAC defined as area under the curve (AUC) of change in worst pain divided by pain measurement duration. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). Change was week x minus baseline.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

152 participants

Primary outcome timeframe

Baseline, Fixed Dosing Date to Day 28 or Early Termination (ET)

Results posted on

2021-01-20

Participant Flow

A0081128 terminated on 01-SEP-2010 due to slow enrollment, analysis at 50 percent (%) enrollment determined that increasing the sample size would require significant extension of enrollment period.

Participant milestones

Participant milestones
Measure	Pregabalin Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo Matching placebo capsules orally twice per day
Overall Study STARTED	72	80
Overall Study COMPLETED	59	59
Overall Study NOT COMPLETED	13	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo Matching placebo capsules orally twice per day
Overall Study Death	3	4
Overall Study Lack of Efficacy	2	4
Overall Study Other	2	2
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	3	3
Overall Study Adverse Event	2	7

Baseline Characteristics

A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=72 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=80 Participants Matching placebo capsules orally twice per day	Total n=152 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	50 Participants n=99 Participants	54 Participants n=107 Participants	104 Participants n=206 Participants
Age, Categorical >=65 years	22 Participants n=99 Participants	26 Participants n=107 Participants	48 Participants n=206 Participants
Sex: Female, Male Female	36 Participants n=99 Participants	41 Participants n=107 Participants	77 Participants n=206 Participants
Sex: Female, Male Male	36 Participants n=99 Participants	39 Participants n=107 Participants	75 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Fixed Dosing Date to Day 28 or Early Termination (ET)

Population: Intent-To-Treat population (ITT): all randomized participants for whom at least one post-baseline efficacy evaluation was obtained; N= the number of participants with evaluable data analyzed; n= number of participants with evaluable data at the specific time point.

Outcome measures

Outcome measures
Measure	Pregabalin n=72 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=79 Participants Matching placebo capsules orally twice per day
Duration Adjusted Average Change (DAAC) From Baseline in Daily Worst Pain, Fixed Dosing Date to Day 28 Baseline (n=72, 79)	6.28 Units on a scale Standard Deviation 1.68	6.47 Units on a scale Standard Deviation 1.59
Duration Adjusted Average Change (DAAC) From Baseline in Daily Worst Pain, Fixed Dosing Date to Day 28 Change at Day 28 (n=72, 77)	-1.53 Units on a scale Standard Deviation 1.81	-1.23 Units on a scale Standard Deviation 1.74

SECONDARY outcome

Timeframe: Baseline, Days 1 through 28 or ET

Population: ITT; N= number of participants with evaluable data analyzed

DAAC from baseline in the daily worst pain based on the NRS Worst Pain at Reference Site score collected from participant's daily diary. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). DAAC defined as AUC of daily worst pain score divided by pain measurement duration. Change was week x minus baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=72 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=77 Participants Matching placebo capsules orally twice per day
DAAC From Baseline in Daily Worst Pain, Days 1 Through 28	-1.27 Units on a scale Standard Deviation 1.45	-1.03 Units on a scale Standard Deviation 1.37

SECONDARY outcome

Timeframe: Baseline, Day 1 to End of Dose Adjustment or ET

Population: ITT; N= number of participants with evaluable data analyzed

Outcome measures

Outcome measures
Measure	Pregabalin n=69 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=76 Participants Matching placebo capsules orally twice per day
DAAC From Baseline in Daily Worst Pain, Day 1 to End of Dose Adjustment	-0.72 Units on a scale Standard Deviation 1.11	-0.53 Units on a scale Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline, 14 Days After Fixed Dosing Date up to Day 28 or ET

Population: ITT; N= number of participants with evaluable data analyzed

DAAC from baseline in the daily worst pain based on the NRS Worst Pain at Reference Site score collected from participant's daily diary 14 days after dosing stabilized (fixed dosing date) up to Day 28. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). DAAC defined as AUC of daily worst pain score divided by pain measurement duration. Change was week x minus baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=72 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=77 Participants Matching placebo capsules orally twice per day
DAAC From Baseline in Daily Worst Pain 14 Days After Fixed Dosing Date Up to Day 28	-1.47 Units on a scale Standard Deviation 1.79	-1.15 Units on a scale Standard Deviation 1.72

SECONDARY outcome

Timeframe: Baseline, Week 4 or ET

Population: ITT; LOCF= Last observation carried forward; n= number of evaluable participants analyzed at each time point; N= number of participants with evaluable data analyzed

m-BPI-sf: participant rated 11-point Likert rating scale ranging from 0 (no pain) to 10 (worst pain possible). Pain severity index was the mean of item scores 1, 2, 3, and 4 (worst, least, average and current pain scores). Change was scores at observation minus scores at baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=71 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=77 Participants Matching placebo capsules orally twice per day
Change From Baseline in Modified Brief Pain Inventory (mBPI-sf) Pain Severity Index Score at Week 4 Baseline (n=71, 77)	5.18 Units on a scale Standard Deviation 1.80	5.03 Units on a scale Standard Deviation 1.72
Change From Baseline in Modified Brief Pain Inventory (mBPI-sf) Pain Severity Index Score at Week 4 Change at Week 4 (n=59, 59)	-2.06 Units on a scale Standard Deviation 1.75	-1.41 Units on a scale Standard Deviation 2.51
Change From Baseline in Modified Brief Pain Inventory (mBPI-sf) Pain Severity Index Score at Week 4 Change at Week 4/LOCF (n=64, 63)	-1.94 Units on a scale Standard Deviation 1.88	-1.35 Units on a scale Standard Deviation 2.54

SECONDARY outcome

Timeframe: Baseline, Week 4 or ET

Population: ITT; LOCF; n= number of evaluable participants analyzed at each time point; N= number of participants with evaluable data analyzed

m-BPI-sf: participant-rated 11 point Likert rating scale ranging from 0 (does not interfere) to 10 (completely intereres) with functional activities (general activity, mood, walking ability, relations with other people, sleep, normal work, and enjoyment of life) in past 24 hours. Change was score at each observation minus baseline score.

Outcome measures

Outcome measures
Measure	Pregabalin n=71 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=76 Participants Matching placebo capsules orally twice per day
Change From Baseline in mBPI-sf Interference Index Score at Week 4 Baseline (n=71, 76)	4.92 Units on a scale Standard Deviation 2.22	5.27 Units on a scale Standard Deviation 2.14
Change From Baseline in mBPI-sf Interference Index Score at Week 4 Change at Week 4 (n=59, 58)	-1.83 Units on a scale Standard Deviation 2.47	-1.50 Units on a scale Standard Deviation 2.44
Change From Baseline in mBPI-sf Interference Index Score at Week 4 Change at Week 4/LOCF(n=64, 62)	-1.66 Units on a scale Standard Deviation 2.57	-1.48 Units on a scale Standard Deviation 2.56

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3 and 4 or ET

Population: Data not analyzed due to early study termination.

Change from baseline in daily average pain score NRS 0 (no pain) to 10 (pain as bad as you can imagine) for pain intensity over past 24 hours recorded every evening before bedtime. Change was week x average minus baseline average.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 0 through Day 28 or ET

Population: Data no analyzed due to early study termination.

Change from baseline in total daily dose of opioids immediate release (IR), sustained release (SR) formulations separately and combined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 0 through Day 28 or ET

Population: Data not analyzed due to early study termination.

IR and SR formulations separately and combined. Change was day x minus baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 4 or ET

Population: ITT; LOCF; n= number of evaluable participants analyzed at each time point; N= number of participants with evaluable data analyzed; individual symptoms not analyzed

HADS: participant rated questionnaire with 2 subscales. HADS-Anxiety assessed generalized anxiety (anxious mood/ restlessness/ anxious thoughts/panic attacks); HADS-Depression assessed lost interest/diminished pleasure response (lowering of hedonic tone). Each subscale has 7 items which ranged from 0 (no presence of anxiety or depression) to 3 (severe feeling anxiety/depression). Total 0-21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. Change was week x minus baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=72 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=78 Participants Matching placebo capsules orally twice per day
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Anxiety Baseline (n= 72, 78)	11.61 Units on a scale Standard Deviation 2.94	11.60 Units on a scale Standard Deviation 2.74
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Anxiety Change at Week 4 (n= 60, 60)	0.98 Units on a scale Standard Deviation 3.31	0.80 Units on a scale Standard Deviation 2.29
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Anxiety Change at Week 4/LOCF (n=64, 65)	0.80 Units on a scale Standard Deviation 3.37	0.71 Units on a scale Standard Deviation 2.42
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Depression Baseline (n= 72, 78)	9.33 Units on a scale Standard Deviation 2.18	10.15 Units on a scale Standard Deviation 2.59
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Depression Change at Week 4 (n= 60, 60)	0.20 Units on a scale Standard Deviation 2.77	-0.57 Units on a scale Standard Deviation 2.13
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 Depression Change at Week 4/LOCF (n=64, 65)	0.22 Units on a scale Standard Deviation 2.73	-0.57 Units on a scale Standard Deviation 2.81

SECONDARY outcome

Timeframe: Weeks 2 and 4 or ET

Population: ITT; LOCF; n=number of evaluable participants analyzed at each time point; N= the number of participants with evaluable data analyzed

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Pregabalin n=69 Participants Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=74 Participants Matching placebo capsules orally twice per day
Patient Global Impression of Change (PGIC) LOCF/ET (n=69, 74)	2.88 Units on a scale Standard Deviation 1.46	2.99 Units on a scale Standard Deviation 1.45
Patient Global Impression of Change (PGIC) Week 2 (n=66,68)	2.97 Units on a scale Standard Deviation 1.36	3.09 Units on a scale Standard Deviation 1.19
Patient Global Impression of Change (PGIC) Week 4 (n=59, 60)	2.73 Units on a scale Standard Deviation 1.39	2.87 Units on a scale Standard Deviation 1.46

SECONDARY outcome

Timeframe: Baseline, Day 14, Day 28 or ET

Population: Data not analyzed due to early study termination.

OR-SDS included OR-SDS individual items by dimension of frequency (rarely to almost constantly), severity (slight to very severe), and degree of bother (not at all to very much), number of episodes of retching/vomiting, OR-SDS dimension composite and overall composite scores. Change was scores at occurance minus score at baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 28 or ET

Population: Data not analyzed due to early study termination.

ECOG - assessed disease progression and how disease affected the daily living abilities of the participant and determined appropriate treatment and prognosis. Graded 0 (fully active able to carry on all pre-disease performance without restrictions) to 5 (dead). Change was day 28 minus baseline.

Outcome measures

Outcome data not reported

Adverse Events

Pregabalin

Serious events: 12 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Pregabalin n=72 participants at risk Pregabalin Flexible Dose 50 to 300 milligrams (mg) capsules orally twice per day (100 to 600 mg/day) for 28 days. Dose adjustments from Day 2 up to Day 14 as needed, followed by fixed dosing through Day 28, followed by dose tapering to Day 34	Placebo n=80 participants at risk Matching placebo capsules orally twice per day
Ear and labyrinth disorders Vertigo	5.6% 4/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	6.9% 5/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.8% 3/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	9.7% 7/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 10/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	8.3% 6/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 4/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	11.1% 8/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 4/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	5.6% 4/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.8% 3/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 4/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 2/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Disturbance in attention	5.6% 4/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	15.3% 11/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.8% 7/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	5.6% 4/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 2/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	25.0% 18/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.5% 6/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Tremor	6.9% 5/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 2/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	0.00% 0/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 4/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 6/72 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 2/80 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER