Trial Outcomes & Findings for Phase IIa: Safety, PK, & Tolerability of Sodium Nitrite in Patients With Peripheral Arterial Disease-SONIC (NCT NCT01401517)
NCT ID: NCT01401517
Last Updated: 2020-04-21
Results Overview
The primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sodium nitrite compared with placebo over a 10 week treatment period. Subjects will be asked to report any adverse events during the trial period, and blood pressure, methemoglobin levels and other blood chemistries will be assessed during the trial period for changes from baseline.
COMPLETED
PHASE2
55 participants
11 weeks
2020-04-21
Participant Flow
Participant milestones
| Measure |
Placebo
sodium nitrite: 0, 40 or 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
40 mg Sodium Nitrite
40 mg dose, BID
sodium nitrite: 0, 40 or 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
80 mg dose, BID
sodium nitrite: 0, 40 or 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
|---|---|---|---|
|
Overall Study
STARTED
|
18
|
19
|
18
|
|
Overall Study
COMPLETED
|
15
|
17
|
15
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase IIa: Safety, PK, & Tolerability of Sodium Nitrite in Patients With Peripheral Arterial Disease-SONIC
Baseline characteristics by cohort
| Measure |
Placebo
n=18 Participants
Placebo twice each day for 11 weeks
|
40 mg Sodium Nitrite
n=19 Participants
40 mg dose, BID
40 mg sodium nitrite: 40 twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=18 Participants
80 mg dose, BID
sodium nitrite: 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
64.9 years
STANDARD_DEVIATION 8.98 • n=5 Participants
|
65.3 years
STANDARD_DEVIATION 8.86 • n=7 Participants
|
67.9 years
STANDARD_DEVIATION 9.99 • n=5 Participants
|
66.0 years
STANDARD_DEVIATION 9.21 • n=4 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
19 participants
n=7 Participants
|
18 participants
n=5 Participants
|
55 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 11 weeksThe primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sodium nitrite compared with placebo over a 10 week treatment period. Subjects will be asked to report any adverse events during the trial period, and blood pressure, methemoglobin levels and other blood chemistries will be assessed during the trial period for changes from baseline.
Outcome measures
| Measure |
40 mg Sodium Nitrite
n=19 Participants
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=18 Participants
80 mg dose, BID
sodium nitrite:80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
Placebo
n=18 Participants
0 mg twice each day for 11 weeks.
|
|---|---|---|---|
|
Reporting of Adverse Events During 11 Week Treatment Period.
at least 1 AE
|
12 participants
|
14 participants
|
9 participants
|
|
Reporting of Adverse Events During 11 Week Treatment Period.
SAEs
|
0 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: Change in flow mediated dilation from baseline to final visit (10 weeks post-treatment)
Demonstrate the pharmacodynamic effect of sodium nitrite on changes in FMD by imaging before investigational product administration and 10 weeks after administration of investigational product but before dose escalation. FMD was measured at baseline and again after 10 weeks of treatment. The value at ten weeks was subtracted from the baseline value. A negative value represents a worsening of FMD while a positive value represents an improvement in FMD.
Outcome measures
| Measure |
40 mg Sodium Nitrite
n=15 Participants
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=16 Participants
80 mg dose, BID
sodium nitrite:80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
Placebo
n=10 Participants
0 mg twice each day for 11 weeks.
|
|---|---|---|---|
|
Assessment of Changes in Brachial Artery Flow-Mediated Dilation (FMD)at 10 Weeks From Baseline
Intent to Treat Population
|
-0.93 percentage from baseline in FMD
Standard Deviation 4.58
|
0.06 percentage from baseline in FMD
Standard Deviation 3.15
|
-2.41 percentage from baseline in FMD
Standard Deviation 6.20
|
|
Assessment of Changes in Brachial Artery Flow-Mediated Dilation (FMD)at 10 Weeks From Baseline
Per Protocol Population
|
-0.69 percentage from baseline in FMD
Standard Deviation 4.65
|
0.50 percentage from baseline in FMD
Standard Deviation 3.28
|
-2.69 percentage from baseline in FMD
Standard Deviation 6.50
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: The change in distance walked in 6 minutes at Day 70 compared to baseline.
Demonstrate the pharmacodynamic effect of sodium nitrite on changes in functional measures of walking distance. The distance a subject can walk in 6 minutes will be measured prior to the first administration of the investigational product and 10 weeks after taking the investigational product but before the dose escalation. Distance walked in 6 minutes was measured at baseline and again after 10 weeks of treatment. The distance walked at ten weeks was subtracted from the baseline distance walked. A negative value represents a worsening of walking distance while a positive value represents an improvement in walking distance.
Outcome measures
| Measure |
40 mg Sodium Nitrite
n=18 Participants
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=17 Participants
80 mg dose, BID
sodium nitrite:80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
Placebo
n=17 Participants
0 mg twice each day for 11 weeks.
|
|---|---|---|---|
|
Assessment of Changes in Walking Distance.
|
47.39 Feet
Standard Deviation 180.46
|
-28.82 Feet
Standard Deviation 259.59
|
7.35 Feet
Standard Deviation 124.67
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: Change in scores on components of quality of life questionnaires at day 70 compared to baseline. The minimum (-100; represents worsening disease) and maximum differences (100, representing complete improvement) from baseline to 10 weeks for the total score of each subsection of the questionnaires are provided.
Demonstrate the pharmacodynamic effect of sodium nitrite on changes in measures of claudication symptoms using Quality of Life questionnaires (WIQ \& RAND SF-36). The WIQ is a disease-specific instrument that measures community-based walking. The questionnaire consists of four subscales (pain severity, distance, speed, and stairs). The SF-36 is a set of 36 questions that the subject provides short answers on concerning general health issues that the subject chooses. Questionnaires were administered at baseline and again after 10 weeks of treatment. Scores from the individual sections were summed and divided by the maximal score for the section to obtain a percent score, ranging from 0 (inability to perform task) to 100 (no difficulty). The scores for each section at ten weeks was subtracted from the baseline scores for each section of the questionnaires. A negative represents declining function, a positive value represents improvement over the study period.
Outcome measures
| Measure |
40 mg Sodium Nitrite
n=18 Participants
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=17 Participants
80 mg dose, BID
sodium nitrite:80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
Placebo
n=17 Participants
0 mg twice each day for 11 weeks.
|
|---|---|---|---|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
WIQ: Walking Distance
|
2.13 units on a scale
Interval -70.3 to 63.4
|
5.05 units on a scale
Interval -66.5 to 61.8
|
-1.07 units on a scale
Interval -14.2 to 45.6
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
WIQ: Walking Speed
|
6.52 units on a scale
Interval -17.4 to 51.5
|
7.07 units on a scale
Interval -57.6 to 28.3
|
0.00 units on a scale
Interval -23.9 to 38.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
WIQ: Stair Climbing
|
12.5 units on a scale
Interval -25.0 to 58.3
|
0.0 units on a scale
Interval -37.5 to 45.8
|
0.0 units on a scale
Interval -41.7 to 45.8
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Physical Functioning
|
5.0 units on a scale
Interval -25.0 to 35.0
|
0.0 units on a scale
Interval -35.0 to 30.0
|
0.0 units on a scale
Interval -20.0 to 15.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Limitations due to Physcial Health
|
0.0 units on a scale
Interval -75.0 to 100.0
|
0.0 units on a scale
Interval -100.0 to 50.0
|
25.0 units on a scale
Interval -75.0 to 50.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Limitations due to Emotional Health
|
0.00 units on a scale
Interval -100.0 to 100.0
|
0.0 units on a scale
Interval -100.0 to 66.7
|
0.0 units on a scale
Interval -100.0 to 100.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Energy/Fatigue
|
0.0 units on a scale
Interval -25.0 to 65.0
|
5.0 units on a scale
Interval -30.0 to 30.0
|
-2.50 units on a scale
Interval -25.0 to 20.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Emotional Well Being
|
2.0 units on a scale
Interval -24.0 to 48.0
|
4.0 units on a scale
Interval -12.0 to 32.0
|
-4.0 units on a scale
Interval -44.0 to 20.0
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Social Functioning
|
0.0 units on a scale
Interval -25.0 to 62.5
|
0.0 units on a scale
Interval -37.5 to 50.0
|
0.0 units on a scale
Interval -25.0 to 12.5
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: Pain
|
12.5 units on a scale
Interval -12.5 to 55.0
|
0.0 units on a scale
Interval -37.5 to 22.5
|
0.0 units on a scale
Interval -55.0 to 22.5
|
|
Assessment of Improvement of Quality of Life Using the WIQ (Walking Impairment Questionnaire) and SF-36 Questionnaire.
SF-36: General Health
|
7.5 units on a scale
Interval -15.0 to 25.0
|
0.0 units on a scale
Interval -20.0 to 30.0
|
0.0 units on a scale
Interval -25.0 to 20.0
|
Adverse Events
Placebo
40 mg Sodium Nitrite
80 mg Sodium Nitrite
Serious adverse events
| Measure |
Placebo
n=18 participants at risk
sodium nitrite: 0 mg twice each day for 11 weeks .
|
40 mg Sodium Nitrite
n=19 participants at risk
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=18 participants at risk
80 mg dose, BID
sodium nitrite: 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
|---|---|---|---|
|
Vascular disorders
Worsening PAD
|
5.6%
1/18 • Number of events 1
|
0.00%
0/19
|
0.00%
0/18
|
|
Gastrointestinal disorders
GI Bleed
|
5.6%
1/18 • Number of events 1
|
0.00%
0/19
|
0.00%
0/18
|
Other adverse events
| Measure |
Placebo
n=18 participants at risk
sodium nitrite: 0 mg twice each day for 11 weeks .
|
40 mg Sodium Nitrite
n=19 participants at risk
40 mg dose, BID
sodium nitrite: 40 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
80 mg Sodium Nitrite
n=18 participants at risk
80 mg dose, BID
sodium nitrite: 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
|
|---|---|---|---|
|
General disorders
Headaches and dizziness
|
0.00%
0/18
|
21.1%
4/19 • Number of events 4
|
44.4%
8/18 • Number of events 8
|
|
Gastrointestinal disorders
GI Disorders
|
22.2%
4/18 • Number of events 4
|
10.5%
2/19 • Number of events 2
|
16.7%
3/18 • Number of events 3
|
|
Infections and infestations
Infections
|
5.6%
1/18 • Number of events 1
|
10.5%
2/19 • Number of events 2
|
5.6%
1/18 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscoskeletal and Connective Tissues
|
11.1%
2/18 • Number of events 2
|
15.8%
3/19 • Number of events 3
|
11.1%
2/18 • Number of events 2
|
|
Investigations
Investigations
|
16.7%
3/18 • Number of events 3
|
5.3%
1/19 • Number of events 1
|
16.7%
3/18 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60