Trial Outcomes & Findings for A Study to Investigate the Analgesic Efficacy of AZD2423 Compared With Placebo After 28 Days Treatment in Patients With Painful Diabetic Polyneuropathy (NCT NCT01201317)

NCT ID: NCT01201317

Last Updated: 2014-04-25

Results Overview

Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Average Pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10; 0=No pain, 10=Worst pain imaginable.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

134 participants

Primary outcome timeframe

Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28

Results posted on

2014-04-25

Participant Flow

The first participant was enrolled on 20th September 2010 and the last participant completed on 6th June 2011. A total of 20 centres in United States (US) and Canada randomised 134 participants.

The study had an enrolment phase of up to 35 days (including wash-out and baseline periods), a 28-day treatment phase, and a follow-up phase of 7-14 days. Participants were randomly assigned to blinded treatment in a 1:1:1 ratio either to AZD2423 20 mg, AZD2423 150 mg or placebo.

Participant milestones

Participant milestones
Measure
AZD2423 150 mg
tablets, 150 mg once daily in the morning
AZD2423 20 mg
tablets, 20 mg once daily in the morning
Placebo
tablets, once daily in the morning
Overall Study
STARTED
48
45
41
Overall Study
COMPLETED
39
38
33
Overall Study
NOT COMPLETED
9
7
8

Reasons for withdrawal

Reasons for withdrawal
Measure
AZD2423 150 mg
tablets, 150 mg once daily in the morning
AZD2423 20 mg
tablets, 20 mg once daily in the morning
Placebo
tablets, once daily in the morning
Overall Study
Withdrawal by Subject
5
0
3
Overall Study
Adverse Event
2
2
2
Overall Study
Screen failure
1
1
0
Overall Study
Protocol Violation
0
1
1
Overall Study
Death
0
1
0
Overall Study
Study-specific withdrawal criteria
0
0
1
Overall Study
Painful Diabetic Neuropathy worsening
0
1
0
Overall Study
Decrease in renal function
0
1
0
Overall Study
Lack of Efficacy
1
0
0
Overall Study
Safety, possible history of tuberculosis
0
0
1

Baseline Characteristics

A Study to Investigate the Analgesic Efficacy of AZD2423 Compared With Placebo After 28 Days Treatment in Patients With Painful Diabetic Polyneuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AZD2423 150 mg
n=48 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=45 Participants
tablets, 20 mg once daily in the morning
Placebo
n=41 Participants
tablets, once daily in the morning
Total
n=134 Participants
Total of all reporting groups
Age, Continuous
57.8 Years
STANDARD_DEVIATION 6.9 • n=99 Participants
59.6 Years
STANDARD_DEVIATION 8.4 • n=107 Participants
56.4 Years
STANDARD_DEVIATION 8.4 • n=206 Participants
58 Years
STANDARD_DEVIATION 8 • n=7 Participants
Sex: Female, Male
Female
23 Participants
n=99 Participants
22 Participants
n=107 Participants
20 Participants
n=206 Participants
65 Participants
n=7 Participants
Sex: Female, Male
Male
25 Participants
n=99 Participants
23 Participants
n=107 Participants
21 Participants
n=206 Participants
69 Participants
n=7 Participants

PRIMARY outcome

Timeframe: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28

Population: Intention-to-treat set (ITT)

Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Average Pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10; 0=No pain, 10=Worst pain imaginable.

Outcome measures

Outcome measures
Measure
AZD2423 150 mg
n=46 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=42 Participants
tablets, 20 mg once daily in the morning
Placebo
n=39 Participants
tablets, once daily in the morning
Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score.
-1.35 Scores on a scale
Standard Deviation 1.89
-1.50 Scores on a scale
Standard Deviation 1.77
-1.61 Scores on a scale
Standard Deviation 2.26

SECONDARY outcome

Timeframe: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28

Population: Intention-to-treat set (ITT)

Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Worst pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10, 0=No pain, 10=Worst pain imaginable.

Outcome measures

Outcome measures
Measure
AZD2423 150 mg
n=46 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=42 Participants
tablets, 20 mg once daily in the morning
Placebo
n=39 Participants
tablets, once daily in the morning
Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score.
-1.57 Scores on a scale
Standard Deviation 1.96
-1.66 Scores on a scale
Standard Deviation 2.06
-1.80 Scores on a scale
Standard Deviation 2.48

SECONDARY outcome

Timeframe: Baseline (mean of Day -5 to Day -1) to Day 28

Population: Intention-to-treat set (ITT)

Last Observation Carried Forward (LOCF). Numerical Rating Scale(NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥30% (yes/no)

Outcome measures

Outcome measures
Measure
AZD2423 150 mg
n=46 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=42 Participants
tablets, 20 mg once daily in the morning
Placebo
n=39 Participants
tablets, once daily in the morning
Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.
16 Participants
19 Participants
15 Participants

SECONDARY outcome

Timeframe: Baseline (mean of Day -5 to Day -1) to Day 28

Population: Intention-to-treat set (ITT)

Last Observation Carried Forward (LOCF). Numerical Rating Scale (NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥50% (yes/no)

Outcome measures

Outcome measures
Measure
AZD2423 150 mg
n=46 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=42 Participants
tablets, 20 mg once daily in the morning
Placebo
n=39 Participants
tablets, once daily in the morning
Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.
10 Participants
8 Participants
10 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 29 (Visit 7)

Population: Modified Intention- to- treat set (ITT) including only patients with adequate baseline and Day 29 data

Last Observation carried Forward (LOCF). Scale consists of 10 Neuropathic Pain Symptom Inventory Scale (NPSI) pain symptom descriptors wiht a recall period of 24 hours. Each descriptor is rated on a Numerical Rating Scale (NRS) 0-10; 0=No (symptom), 10=Worst (symptom) imaginable. The NPSI Total Score was calculated as the sum of 10 of the NPSI descriptors. Range for total score 0 -100. Higher total score implicates worse symptoms.

Outcome measures

Outcome measures
Measure
AZD2423 150 mg
n=35 Participants
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=30 Participants
tablets, 20 mg once daily in the morning
Placebo
n=33 Participants
tablets, once daily in the morning
Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score.
-14.63 Scores on a scale
Standard Deviation 22.77
-12.20 Scores on a scale
Standard Deviation 22.84
-7.82 Scores on a scale
Standard Deviation 17.02

Adverse Events

AZD2423 150 mg

Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths

AZD2423 20 mg

Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
AZD2423 150 mg
n=47 participants at risk
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=44 participants at risk
tablets, 20 mg once daily in the morning
Placebo
n=41 participants at risk
tablets, once daily in the morning
Respiratory, thoracic and mediastinal disorders
Asthma
0.00%
0/47
Safety analysis set
2.3%
1/44
Safety analysis set
0.00%
0/41
Safety analysis set
Infections and infestations
Clostridium difficile colitis
0.00%
0/47
Safety analysis set
2.3%
1/44
Safety analysis set
0.00%
0/41
Safety analysis set
Cardiac disorders
Myocardial Infarction
0.00%
0/47
Safety analysis set
2.3%
1/44
Safety analysis set
0.00%
0/41
Safety analysis set
General disorders
Sudden cardiac death
0.00%
0/47
Safety analysis set
2.3%
1/44
Safety analysis set
0.00%
0/41
Safety analysis set

Other adverse events

Other adverse events
Measure
AZD2423 150 mg
n=47 participants at risk
tablets, 150 mg once daily in the morning
AZD2423 20 mg
n=44 participants at risk
tablets, 20 mg once daily in the morning
Placebo
n=41 participants at risk
tablets, once daily in the morning
Nervous system disorders
Headache
6.4%
3/47
Safety analysis set
0.00%
0/44
Safety analysis set
2.4%
1/41
Safety analysis set
Nervous system disorders
Dizziness
4.3%
2/47
Safety analysis set
2.3%
1/44
Safety analysis set
2.4%
1/41
Safety analysis set
Gastrointestinal disorders
Nausea
4.3%
2/47
Safety analysis set
2.3%
1/44
Safety analysis set
2.4%
1/41
Safety analysis set
General disorders
Pyrexia
4.3%
2/47
Safety analysis set
2.3%
1/44
Safety analysis set
0.00%
0/41
Safety analysis set
Musculoskeletal and connective tissue disorders
Arthralgia
4.3%
2/47
Safety analysis set
0.00%
0/44
Safety analysis set
0.00%
0/41
Safety analysis set
Infections and infestations
Upper respiratory tract infection
4.3%
2/47
Safety analysis set
0.00%
0/44
Safety analysis set
0.00%
0/41
Safety analysis set
Gastrointestinal disorders
Diarrhoea
2.1%
1/47
Safety analysis set
4.5%
2/44
Safety analysis set
7.3%
3/41
Safety analysis set
Musculoskeletal and connective tissue disorders
Muscle spasms
0.00%
0/47
Safety analysis set
2.3%
1/44
Safety analysis set
7.3%
3/41
Safety analysis set
Skin and subcutaneous tissue disorders
Pruritus
0.00%
0/47
Safety analysis set
0.00%
0/44
Safety analysis set
4.9%
2/41
Safety analysis set

Additional Information

Heather Bryson

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee No such publication or presentation may include any of AstraZeneca's Confidential Information without AstraZeneca's prior written approval. AZ should have 60 days for review and can extend time until submission up to 90 days.
  • Publication restrictions are in place

Restriction type: OTHER