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

A Phase 3 Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of NKTR-181 in Opioid-Naive Subjects With Moderate to Severe Chronic Low Back Pain

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02362672

Acronym

SUMMIT-07

Enrollment

1189

Registered

2015-02-13

Start date

2015-03-11

Completion date

2017-02-28

Last updated

2020-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Pain, Low Back Pain

Brief summary

The purpose of this study is to determine whether a new opioid molecule, NKTR-181, is effective for the relief of moderate to severe chronic low back pain as compared to a placebo.

Detailed description

This is an enriched enrollment, randomized withdrawal study with an open label, dose-titration period followed by a randomized, double-blind, placebo-control treatment of twelve weeks. During the double-blind treatment period, this study will evaluate the analgesic effect of NKTR-181 versus placebo in patients with moderate to severe chronic low back pain.

Interventions

DRUGNKTR-181 BID tablets

NKTR-181 tablets 100-400 mg twice daily (BID)

DRUGPlacebo to match NKTR-181 BID tablets

Placebo to match NKTR-181 tablets 100-400 mg twice daily (BID)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Male or non-pregnant, non-nursing female aged 18 to 75 years old * Clinical diagnosis of moderate to severe, chronic non-neuropathic low back pain for at least six months * Not experiencing adequate pain relief or have failed previous treatment with non-opioid analgesics * Opioid analgesia is necessary * Currently taking no more than 10 mg morphine sulfate equivalents per day of short acting opioids for 14 days prior to entry * Females of child bearing potential must be using a highly effective form of birth control. All subjects must agree to use double-barrier contraception during participation in this study and for at least 2 months after the last dose of the study drug. * Willing and able to provide informed consent

Exclusion criteria

* Taking extended release or long-acting opioids within 6 months * History of hypersensitivity, intolerance, or allergy to opioids * Compression of spinal nerve root; spinal fracture, tumor, or abscess * Surgical procedures on the low back in the last 12 months or facet nerve root block or radiofrequency ablation in the last 3 months * Untreated moderate to severe sleep apnea

Design outcomes

Primary

Measure	Time frame	Description
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)	12 Weeks of randomized double blinded period	The daily pain intensity is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

Secondary

Measure	Time frame	Description
Responder Analysis Based on Percent Reduction in Pain Intensity	Screening Baseline through Week 12	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.
Patient Global Impression of Change (PGIC): Number of Responders	Screening Baseline through Week 12	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.
Change in Sleep Quality in the Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R)	Screening Baseline through Week 12	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.
Change in Sleep Quantity Measure in Hours in the Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R)	Screening Baseline through Week 12	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.
Change in Roland Morris Disability Questionnaire (RMDQ)	Screening Baseline through Week 12	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.

Countries

United States

Participant flow

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.

Participants by arm

Arm	Count
NKTR-181 NKTR-181 (Double-blind Treatment Phase)	309
Placebo Placebo (Double-blind Treatment Phase)	301
Total	610

Baseline characteristics

Characteristic	NKTR-181	Total	Placebo
Age, Continuous	52.0 years STANDARD_DEVIATION 12.7	51.4 years STANDARD_DEVIATION 12.6	50.7 years STANDARD_DEVIATION 12.5
Race (NIH/OMB) American Indian or Alaska Native	3 Participants	6 Participants	3 Participants
Race (NIH/OMB) Asian	4 Participants	6 Participants	2 Participants
Race (NIH/OMB) Black or African American	95 Participants	188 Participants	93 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	6 Participants	4 Participants
Race (NIH/OMB) White	205 Participants	401 Participants	196 Participants
Screening Baseline Pain Intensity in Numeric Rating Scale (NRS)	6.7 units on a scale STANDARD_DEVIATION 0.9	6.73 units on a scale STANDARD_DEVIATION 0.9	6.8 units on a scale STANDARD_DEVIATION 0.9
Sex: Female, Male Female	187 Participants	357 Participants	170 Participants
Sex: Female, Male Male	122 Participants	253 Participants	131 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	803 / 1,189	111 / 309	66 / 301
serious Total, serious adverse events	9 / 1,189	5 / 309	6 / 301

Outcome results

Primary

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)

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

Population: The analysis set (N=610) is the intention-to-treat population, which was defined as all randomized subjects

Arm	Measure	Value (MEAN)	Dispersion
NKTR-181	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)	0.9 units on a scale	Standard Error 0.11
Placebo	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)	1.5 units on a scale	Standard Error 0.11

Comparison: NKTR-181 (Double-blind Treatment Phase), Placebo (Double-blind Treatment Phase)p-value: 0.0019z-test

Secondary

Change in Roland Morris Disability Questionnaire (RMDQ)

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.