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Efficacy and Safety Study of NKTR-181 in Opioid-Naive Subjects With Low Back Pain (SUMMIT-07)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02362672
Recruitment Status : Completed
First Posted : February 13, 2015
Results First Posted : September 16, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Low Back Pain
Chronic Pain
Interventions Drug: NKTR-181 BID tablets
Drug: Placebo to match NKTR-181 BID tablets
Enrollment 1189
Recruitment Details First subject screened: 11Mar2015; Last subject out: 28 Dec 2016. The study was conducted at 55 medical/research sites in the United States.
Pre-assignment Details The titration phase of the study was designed to titrate patients to a dose of NKTR-181 that provided adequate analgesia and acceptable side effects.
Arm/Group Title NKTR-181 (Open-label Titration Phase) NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase)
Hide Arm/Group Description NKTR-181 100-400 mg twice daily tablets NKTR-181: 100-400 mg twice daily tablets Placebo: Placebo, twice daily tablets
Period Title: Titration Phase
Started 1189 0 0
Completed 610 0 0
Not Completed 579 0 0
Period Title: Double-blind Maintenance Phase
Started 0 309 301
Completed 0 249 242
Not Completed 0 60 59
Arm/Group Title NKTR-181 Placebo Total
Hide Arm/Group Description NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase) Total of all reporting groups
Overall Number of Baseline Participants 309 301 610
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 309 participants 301 participants 610 participants
52.0  (12.7) 50.7  (12.5) 51.4  (12.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 309 participants 301 participants 610 participants
Female
187
  60.5%
170
  56.5%
357
  58.5%
Male
122
  39.5%
131
  43.5%
253
  41.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 309 participants 301 participants 610 participants
American Indian or Alaska Native
3
   1.0%
3
   1.0%
6
   1.0%
Asian
4
   1.3%
2
   0.7%
6
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
   0.7%
2
   0.3%
Black or African American
95
  30.7%
93
  30.9%
188
  30.8%
White
205
  66.3%
196
  65.1%
401
  65.7%
More than one race
0
   0.0%
1
   0.3%
1
   0.2%
Unknown or Not Reported
2
   0.6%
4
   1.3%
6
   1.0%
Screening Baseline Pain Intensity in Numeric Rating Scale (NRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 309 participants 301 participants 610 participants
6.7  (0.9) 6.8  (0.9) 6.73  (0.9)
[1]
Measure Description:

The pain intensity in NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

Screening baseline was the 7-day average immediately prior to the first dose of NKTR-181
1.Primary Outcome
Title The Change in Weekly (ie, 7-day Average) Pain Score at the End of Double-blind, Randomized Treatment Period, Relative to the Weekly Score at the End of Titration (Double-blind Baseline)
Hide Description The daily pain intensity is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).
Time Frame 12 Weeks of randomized double blinded period
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set (N=610) is the intention-to-treat population, which was defined as all randomized subjects
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind Treatment Phase)
Placebo (Double-blind Treatment Phase)
Overall Number of Participants Analyzed 309 301
Mean (Standard Error)
Unit of Measure: units on a scale
0.9  (0.11) 1.5  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-181, Placebo
Comments NKTR-181 (Double-blind Treatment Phase), Placebo (Double-blind Treatment Phase)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.55
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Responder Analysis Based on Percent Reduction in Pain Intensity
Hide Description A responder is defined by the Sponsor as a randomized subject who completes the double-blind Randomized Treatment Period and experiences improvement in the Week 12 Weekly Pain Score from Screening Pain Score. This includes the proportion of responders with at least 30% and at least 50% reduction in pain intensity.
Time Frame Screening Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind Treatment Phase)
Placebo (Double-blind Treatment Phase)
Overall Number of Participants Analyzed 309 301
Measure Type: Count of Participants
Unit of Measure: Participants
Subjects with 30% improvement
220
  71.2%
172
  57.1%
Subjects with 50% improvement
158
  51.1%
114
  37.9%
3.Secondary Outcome
Title Patient Global Impression of Change (PGIC): Number of Responders
Hide Description The PGIC assesses the change in overall status relative to the initiation of the treatment. The scale measures global change of overall status on a 7-point scale (1 = No change (or condition has got worse), 2 = Almost the same, 3 = A little better, 4 = Somewhat better, 5 = Moderately better, 6 = Better, 7 = A great deal better). The proportion of subjects responding " A great deal better " and "better" was summarized by treatment group.
Time Frame Screening Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind treatment phase)
Placebo (Double-blind treatment phase)
Overall Number of Participants Analyzed 309 301
Measure Type: Count of Participants
Unit of Measure: Participants
159
  51.5%
100
  33.2%
4.Secondary Outcome
Title Change in Sleep Quality in the Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R)
Hide Description The MOS Sleep Scale measure sleep parameters contains 12 items. Eleven of them scored using a 5-point response scale and across 5 dimensions of sleep, including disturbance (4 items), sleep problems index (9 items), somnolence (3 items), adequacy (2 items), and respiratory impairments (2 items). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Items in each dimension (disturbance, sleep problems index, somnolence, adequacy, respiratory impairments) of sleep are averaged together to create the score for the scale. The range of each sleep dimension is from 0 to 100. Higher score of sleep disturbance, somnolence, sleep indices, and respiratory impairments indicates relatively worse sleep problem, whereas lower scores for sleep adequacy indicate worse sleep problems.
Time Frame Screening Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The MOS Sleep-R was analyzed and presented as a change from Screening Baseline to Week 12 in double blinded treatment period. Subjects who discontinued from treatment early were not included in this analysis.
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind Treatment Phase)
Placebo (Double-blind Treatment Phase)
Overall Number of Participants Analyzed 254 253
Mean (Standard Deviation)
Unit of Measure: units on a scale
Sleep Disturbance -16.7  (23.9) -9.5  (22.8)
Sleep Problems Index -11.6  (18.9) -6.9  (18.4)
Respiratory Impairments -3.5  (18.9) -2.2  (18.6)
Sleep Adequacy 9.1  (26.1) 4.0  (25.6)
Somnolence -6.1  (21.0) -7.4  (21.8)
5.Secondary Outcome
Title Change in Sleep Quantity Measure in Hours in the Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R)
Hide Description The 12 items of the MOS Sleep Scale measure sleep parameters across 6 dimensions of sleep, including disturbance (4 items), sleep problems index (9 items), quantity (1 item), somnolence (3 items), adequacy (2 items), and respiratory impairments (2 items). One of the 12 items, Sleep quantity, records the actual number of hours slept. Reported here is the sleep quantity.
Time Frame Screening Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind Treatment Phase)
Placebo (Double-blind Treatment Phase)
Overall Number of Participants Analyzed 254 253
Mean (Standard Deviation)
Unit of Measure: hours
0.3  (1.1) 0.2  (1.2)
6.Secondary Outcome
Title Change in Roland Morris Disability Questionnaire (RMDQ)
Hide Description

The RMDQ contains 24 items that is used to quantify the impact of low back pain on subject's ability to perform daily activities, mood and sleep. The questionnaire consists of 24 statements derived from the Sickness Impact Profile, with the addition of the phrase "because of my back." The questionnaire covers the areas of mobility, self-care, and sleeping.

The RMDQ score is the total number of items checked which is from a minimum of 0 to a maximum of 24; the greater the score the grater the physical disability due to lower back pain.
Time Frame Screening Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The RMDQ was analyzed and presented as a change from Screening Baseline to Week 12 in double blinded treatment period. Subjects who discontinued from treatment early were not included in this analysis.
Arm/Group Title NKTR-181 Placebo
Hide Arm/Group Description:
NKTR-181 (Double-blind Treatment Phase)
Placebo (Double-blind Treatment Phase)
Overall Number of Participants Analyzed 254 253
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.0  (5.7) -3.5  (5.6)
Time Frame Adverse events were reported starting immediately after the subject provided written informed consent through the end of study, which is approximately 20 to 25 weeks for each subject.
Adverse Event Reporting Description Adverse events were collected after the subject provided written informed consent till the end of study through spontaneous reports or were observed during other assessments. All ongoing AEs were followed until resolution or for 14 days after the subject's last visit, whichever came first. All SAEs were followed until resolution, stabilization of condition, return to baseline, or until follow-up is no longer possible.
 
Arm/Group Title NKTR-181 (Titration Phase) NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase)
Hide Arm/Group Description NKTR-181 100-400 mg twice daily tablets NKTR-181 100-400 mg twice daily tablets Placebo, twice daily tablets
All-Cause Mortality
NKTR-181 (Titration Phase) NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
NKTR-181 (Titration Phase) NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/1189 (0.76%)   5/309 (1.62%)   6/301 (1.99%) 
Cardiac disorders       
Atrial Fibrillation † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Eye disorders       
Blindness transient † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Gastrointestinal disorders       
Large intestine perforation † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Diverticulum intestinal † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
General disorders       
Chest Pain † 1  0/1189 (0.00%)  1/309 (0.32%)  0/301 (0.00%) 
Infections and infestations       
Cellulitis † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Gastrointestinal infection † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Herpes virus infection † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Infective exacerbation of chronic obstructive airways † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Pneumonia † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Diverticulitis † 1  0/1189 (0.00%)  1/309 (0.32%)  0/301 (0.00%) 
Bacterial infection † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
Gastroenteritis † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
Injury, poisoning and procedural complications       
Rib fracture † 1  0/1189 (0.00%)  1/309 (0.32%)  0/301 (0.00%) 
Skin abrasions † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder cancer † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
Dysarthria † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
Nervous system disorders       
Cerebrovascular accident † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Renal and urinary disorders       
Renal failure † 1  0/1189 (0.00%)  1/309 (0.32%)  0/301 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary Embolism † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Skin and subcutaneous tissue disorders       
Angiodema † 1  1/1189 (0.08%)  0/309 (0.00%)  0/301 (0.00%) 
Vascular disorders       
Hypertension † 1  0/1189 (0.00%)  1/309 (0.32%)  0/301 (0.00%) 
Malignant hypertension † 1  0/1189 (0.00%)  0/309 (0.00%)  1/301 (0.33%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NKTR-181 (Titration Phase) NKTR-181 (Double-blind Treatment Phase) Placebo (Double-blind Treatment Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   803/1189 (67.54%)   111/309 (35.92%)   66/301 (21.93%) 
Gastrointestinal disorders       
Constipation † 1  425/1189 (35.74%)  27/309 (8.74%)  9/301 (2.99%) 
Nausea † 1  176/1189 (14.80%)  32/309 (10.36%)  18/301 (5.98%) 
Vomiting † 1  67/1189 (5.63%)  15/309 (4.85%)  5/301 (1.66%) 
Dry mouth † 1  66/1189 (5.55%)  7/309 (2.27%)  1/301 (0.33%) 
Diarrhoea † 1  35/1189 (2.94%)  8/309 (2.59%)  17/301 (5.65%) 
General disorders       
Fatigue † 1  61/1189 (5.13%)  4/309 (1.29%)  1/301 (0.33%) 
Nervous system disorders       
Somnolence † 1  107/1189 (9.00%)  8/309 (2.59%)  1/301 (0.33%) 
Headache † 1  83/1189 (6.98%)  10/309 (3.24%)  14/301 (4.65%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a joint manuscript has not been submitted for publication within twelve (12) months of completion or termination of the study, the PI is free to publish separately, upon provision of any proposed publication or manuscript to the Sponsor at least sixty (60) days before it is submitted or otherwise disclosed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Affairs
Organization: Nektar Therapeutics
EMail: StudyInquiry@nektar.com
Publications of Results:
Markman J, Gudin J, Rauck R, Argoff C, Rowbotham M, Agaiby E, Gimbel J, Katz N, Doberstein SK, Tagliaferri M, Lu L, Siddhanti S, Hale M. SUMMIT-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain. Pain. 2019 Jun;160(6):1374-1382. doi: 10.1097/j.pain.0000000000001517.
Layout table for additonal information
Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT02362672    
Other Study ID Numbers: 14-181-07
First Submitted: February 9, 2015
First Posted: February 13, 2015
Results First Submitted: December 19, 2019
Results First Posted: September 16, 2020
Last Update Posted: September 16, 2020