Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1 (NCT NCT00109772)

Last Updated: 2013-08-28

Results Overview

Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Responders are participants who completed 12 weeks of treatment and their week 12 PI-NRS score showed at least a 30% improvement from baseline. Participants who did not complete 12 weeks of treatment are considered non-responders.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

184 participants

Primary outcome timeframe

Day 0, Week 12

Results posted on

2013-08-28

Participant Flow

A total of 184 participants were randomized to the study and 180 participants received at least 1 dose of study drug.

Participant milestones

Participant milestones
Measure	Lenalidomide 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Double-blind Treatment STARTED	90	94
Double-blind Treatment Safety and ITT Population	87	93
Double-blind Treatment COMPLETED	68	79
Double-blind Treatment NOT COMPLETED	22	15
Open-label Extension STARTED	64	78
Open-label Extension COMPLETED	19	29
Open-label Extension NOT COMPLETED	45	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenalidomide 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Double-blind Treatment Adverse Event	14	5
Double-blind Treatment Lack of Efficacy	1	0
Double-blind Treatment Withdrawal by Subject	2	1
Double-blind Treatment Lost to Follow-up	2	3
Double-blind Treatment Protocol Violation	0	1
Double-blind Treatment Other	0	4
Double-blind Treatment Withdrew prior to treatment	3	1
Open-label Extension Adverse Event	10	19
Open-label Extension Lack of Efficacy	19	11
Open-label Extension Withdrawal by Subject	9	6
Open-label Extension Lost to Follow-up	1	0
Open-label Extension Death	0	1
Open-label Extension Protocol Violation	2	2
Open-label Extension Other	4	10

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide n=87 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Total n=180 Participants Total of all reporting groups
Age Continuous	43.9 years STANDARD_DEVIATION 11.37 • n=5 Participants	45.1 years STANDARD_DEVIATION 11.06 • n=7 Participants	44.5 years STANDARD_DEVIATION 11.20 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	79 Participants n=7 Participants	144 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	14 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized White	81 participants n=5 Participants	86 participants n=7 Participants	167 participants n=5 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0, Week 12

Population: Intent to treat

Outcome measures

Outcome measures
Measure	Lenalidomide n=87 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Percentage of Participants Who Have a >= 30% Reduction (Improvement) in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score From Baseline to the Last Assessment Responders	16.1 percentage of participants	16.1 percentage of participants
Percentage of Participants Who Have a >= 30% Reduction (Improvement) in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score From Baseline to the Last Assessment Non-responders	83.9 percentage of participants	83.9 percentage of participants

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat. Last observation carried forward. Three participants had no post-treatment values.

Short Form McGill Pain Questionnaire (SF-MPQ) is comprised of 15 pain qualities that are rated by the participant on a 4 point scale with 0=none and 3=severe. The scale for the Total Score is 0-45. Week 12 values are compared to baseline values. Negative changes indicate improvement in level of pain.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Total Score of the Short Form McGill Pain Questionnaire (SF-MPQ) at Week 12	-5.2 units on a scale Standard Deviation 9.15	-3.0 units on a scale Standard Deviation 9.37

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. Morning and evening scores are averaged. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Week 12 values are compared to baseline values. Negative changes indicate improvement in level of pain.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score Using Averaged Morning and Evening Readings at Week 12	-0.6 units on a scale Standard Deviation 1.65	-0.4 units on a scale Standard Deviation 1.50

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. The morning pain ratings at baseline and Week 12 are compared. Negative changes indicate improvement in level of pain.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Morning Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12	-0.6 units on a scale Standard Deviation 1.67	-0.4 units on a scale Standard Deviation 1.53

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. The evening pain ratings at baseline and Week 12 are compared. Negative changes indicate improvement in level of pain.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Evening Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12	-0.6 units on a scale Standard Deviation 1.69	-0.4 units on a scale Standard Deviation 1.53

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants rated how much CRPS pain interfered with their sleep each day in a diary. The Sleep Assessment uses an eleven point scale for four questions. Questions concern ability to fall asleep, ability to stay asleep, how refreshed the participant feels upon waking and how alert the participant is during the day. All use a scale of 0-10, where the higher number is the positive response (e.g. 0=Pain completely interferes with sleep and 10=Pain does not interfere). The mean of all four responses was calculated if at least 3 of the 4 questions had a value. Week 12 values are compared to baseline values. Positive change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in Daily Sleep Assessment Average Score at Week 12	0.7 units on a scale Standard Deviation 1.48	0.7 units on a scale Standard Deviation 1.42

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants rated how the activity level on a given day compares with their activity level prior to the start of treatment. A seven-point scale is used with -3=much worse and +3=much better. Positive change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in Activity Level Rating Using a Numeric Rating Scale (NRS) at Week 12	0.1 units on a scale Standard Deviation 1.08	0.2 units on a scale Standard Deviation 1.09

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Thirty-three participants had either no baseline or post-treatment values.

Participants rated twelve CRPS symptoms using a four-point rating scale in which 1=the most positive outcome and 4= the most negative outcome for a total scale of 12-48. Week 12 values are compared to baseline values. Negative change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=67 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=80 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in Participant Assessment of CRPS Symptoms Total Score at Week 12	-2.4 units on a scale Standard Deviation 6.27	-1.4 units on a scale Standard Deviation 5.83

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Sixteen participants had either no baseline or post-treatment values.

The investigator rated the degree of allodynia on both the CRPS-affected limb on an eleven-point scale where 0=no pain and 10=worst pain imaginable. This outcome compares the baseline values for the CRPS affected-limb to the values at week 12. Negative change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=76 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=86 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in "Mechanically Evoked" (Allodynia) Numeric Rating Scale (NRS) Score at Week 12	-0.8 units on a scale Standard Deviation 2.38	-0.1 units on a scale Standard Deviation 2.64

SECONDARY outcome

Timeframe: Week 12

Population: Intent to treat population. Last observation carried forward. Fifteen participants were missing values.

The investigator rated the degree of allodynia on both the CRPS-affected limb and the normal (or less-affected) limb on an eleven-point scale where 0=no pain and 10=worst pain imaginable. This outcome compares the values for the CRPS affected-limb to the normal limb at week 12.

Outcome measures

Outcome measures
Measure	Lenalidomide n=76 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=87 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Difference in Allodynia Rating Between the CRPS-affected Limb and the Normal Limb at Week 12	3.7 units on a scale Standard Deviation 3.23	4.1 units on a scale Standard Deviation 3.41

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Three participants had no post-treatment values.

Participants completed the Brief Pain Inventory which asks twelve questions that are rated on an eleven-point scale in which 0=most positive outcome and 10=the most negative outcome for a total scale of 0-120. BPI contains questions that concern the level of pain over the last week and the level of pain right now, the extent to which pain interfered with sleep, normal activities, ability to work, relationships, walking etc. Week 12 values are compared to baseline values. Negative change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=85 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=92 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Brief Pain Inventory (BPI) Total Score at Week 12	-4.8 units on a scale Standard Deviation 13.03	-3.7 units on a scale Standard Deviation 12.22

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Last observation carried forward. Six participants had no post-treatment values.

Participants completed the Profile of Mood States questionnaire that asks participants to rate how each of 65 words reflected their mood in the past week on a 5-point scale with 0=not at all and 4=extremely for a total scale of 0-260. Week 12 values are compared to baseline values. Negative change values indicate improvement.

Outcome measures

Outcome measures
Measure	Lenalidomide n=84 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=90 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Profile of Mood States (POMS) at Week 12	-9.6 units on a scale Standard Deviation 33.99	-4.5 units on a scale Standard Deviation 33.91

SECONDARY outcome

Timeframe: Week 12

Population: Intent to treat. Forty-five participants had no week 12 values.

The Patient Global Impression of Change asks the question: Overall, how would you rate your CRPS condition since the start of study drug? Answers are represented on a seven-point scale with -3=much worst and +3=much better.

Outcome measures

Outcome measures
Measure	Lenalidomide n=61 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=74 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Patient Global Impression of Change (PGIC) at Week 12	0.2 units on a scale Standard Deviation 1.45	0.2 units on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: Day 1 to week 12

Population: Intent to treat population

Participants who had any change in CRPS medication during the double-blind treatment period (up to week 12) are summarized. Changes include additions, discontinuations or dosage change of CRPS medication(s).

Outcome measures

Outcome measures
Measure	Lenalidomide n=87 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Participants Who Had a Change to CRPS Pain Medication During the Treatment Period Change to CRPS medication(s)	11 participants	7 participants
Participants Who Had a Change to CRPS Pain Medication During the Treatment Period No change to CRPS medication	76 participants	86 participants

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Fifty participants did not have week 12 values.

An electrophysiological evaluation using standard electrophysiological and electromyography to measure the speed and extent of nerve conduction. Week 12 values are compared to baseline values for maximal motor nerve conduct velocity.

Outcome measures

Outcome measures
Measure	Lenalidomide n=57 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=73 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Maximal Composite Motor Nerve Conduction Velocity at Week 12	0.3 meters/second Standard Deviation 1.56	0.1 meters/second Standard Deviation 2.14

SECONDARY outcome

Timeframe: Day 0, week 12

Population: Intent to treat population. Fifty participants did not have week 12 values.

Outcome measures

Outcome measures
Measure	Lenalidomide n=56 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=74 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Change From Baseline in the Maximal Composite Sensory Nerve Conduction Velocity at Week 12	1.2 meters/second Standard Deviation 3.51	0.1 meters/second Standard Deviation 3.41

SECONDARY outcome

Timeframe: Day 1 up to week 158

Population: Safety population

Counts of study participants who had adverse events (AEs) while treated in either the Double-blind or Extension Periods. The NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 was used by the investigator to grade the severity of the AEs: Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE, Grade 5=Death related to AE. AEs are also summarized by whether they were serious, related to treatment and whether the AE caused treatment to be altered. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event could have jeopardized the patient's safety or required medical or surgical intervention to prevent one of the outcomes listed above.

Outcome measures

Outcome measures
Measure	Lenalidomide n=87 Participants 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 Participants Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Adverse event (AE)	83 participants	85 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Serious adverse event (SAE)	12 participants	16 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period AE leading to study drug discontinuation	29 participants	29 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period AE leading to dose reduction or interruption	10 participants	8 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Treatment-related AE	68 participants	66 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Treatment-related SAE	1 participants	5 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Grade 2 or higher AE	63 participants	68 participants
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period Grade 3 or higher AE	15 participants	18 participants

Adverse Events

Lenalidomide

Serious events: 12 serious events

Other events: 77 other events

Deaths: 0 deaths

Placebo to Lenalidomide

Serious events: 16 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER

Measure	Lenalidomide n=87 participants at risk 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 participants at risk Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Injury, poisoning and procedural complications Joint sprain	2.3% 2/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Injury, poisoning and procedural complications Foot fracture	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Vascular disorders Deep vein thrombosis	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	2.2% 2/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Vascular disorders Thrombosis	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Investigations Blood human chorionic gonadotropin positive	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Investigations Blood potassium decreased	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Investigations Blood pressure diastolic increased	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Investigations Pregnancy test false positive	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Nervous system disorders Neuropathic pain	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Nervous system disorders Tremor	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Cardiac disorders Bradycardia NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Cardiac disorders Sick sinus syndrome	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Endocrine disorders Adrenal insufficiency NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Endocrine disorders Thyroiditis NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Hepatobiliary disorders Cholecystitis NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Hepatobiliary disorders Gallbladder obstruction	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Pregnancy, puerperium and perinatal conditions Pregnancy NOS	2.3% 2/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous NOS	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Respiratory, thoracic and mediastinal disorders Alveolitis allergic	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Blood and lymphatic system disorders Hemolytic anemia NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Vomiting NOS	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
General disorders Pain NOS	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Infections and infestations Clostridium colitis	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Musculoskeletal and connective tissue disorders Arthritis NOS	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Reproductive system and breast disorders Endometriosis	0.00% 0/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Skin and subcutaneous tissue disorders Angioneurotic edema	1.1% 1/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	0.00% 0/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.

Measure	Lenalidomide n=87 participants at risk 10 mg/day lenalidomide orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of continuing on lenalidomide in the open-label extension period for as long as benefit was derived from the drug or until study closure.	Placebo to Lenalidomide n=93 participants at risk Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
Skin and subcutaneous tissue disorders Rash NOS	27.6% 24/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	9.7% 9/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Skin and subcutaneous tissue disorders Pruritus	9.2% 8/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	4.3% 4/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Skin and subcutaneous tissue disorders Contusion	3.4% 3/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	6.5% 6/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Skin and subcutaneous tissue disorders Dry skin	6.9% 6/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	2.2% 2/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Nausea	16.1% 14/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	16.1% 15/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Diarrhoea NOS	12.6% 11/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	10.8% 10/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Constipation	9.2% 8/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	5.4% 5/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Gastrointestinal disorders Vomiting NOS	5.7% 5/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	4.3% 4/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Nervous system disorders Headache	10.3% 9/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	14.0% 13/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Nervous system disorders Dizziness	10.3% 9/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	6.5% 6/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
General disorders Fatigue	10.3% 9/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	12.9% 12/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
General disorders Pyrexia	6.9% 6/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	4.3% 4/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
General disorders Fall	3.4% 3/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	5.4% 5/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	6.9% 6/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	5.4% 5/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Respiratory, thoracic and mediastinal disorders Pharyngitis	6.9% 6/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	4.3% 4/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Infections and infestations Urinary tract infection NOS	3.4% 3/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	6.5% 6/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Infections and infestations Sinusitis NOS	5.7% 5/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	3.2% 3/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Investigations Alanine aminotransferase increased	5.7% 5/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	1.1% 1/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Musculoskeletal and connective tissue disorders Muscle cramp	5.7% 5/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	4.3% 4/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.
Psychiatric disorders Insomnia	8.0% 7/87 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.	5.4% 5/93 • Day 1 up to week 158, covering both the double-blind treatment and extension periods. If multiple SAEs were reported within a given preferred term, only one event was counted per subject.