Diabetes
Conditions
Keywords
neuropathy
Brief summary
In this study, subjects with diabetic neuropathic pain (DNP) will be treated for 12 weeks with either placebo, 40 or 80 mg sustained release sodium nitrite (TV1001sr) twice daily. Primary endpoints will be safety and pharmacokinetics. Assessment of the study medications affects on pain following treatment will also be recorded.
Detailed description
This is a dose-ranging study to evaluate the safety, pharmacokinetics, and tolerability of multiple doses of an oral, sustained release formulation of sodium nitrite (TV1001sr) in subjects with DNP. The primary objective is to assess the safety and tolerability of multiple doses of twice daily 40 mg and 80 mg TV1001sr compared with placebo over a 12 week treatment period and the pharmacokinetics of the sustained release formulation of sodium nitrite. Secondary objectives are to evaluate the pharmacokinetics and markers of functional improvement including pain questionnaires, quantitative sensory testing and changes in markers of diabetes.
Interventions
DRUGSodium nitrite
Sustained release formulation of sodium nitrite
DRUGPlacebo
Placebo tablets containing same excipients and coatings used in the active tablets, without sodium nitrite being added.
Sponsors
Kettering Health Network
TheraVasc Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Female subjects must be post-menopausal, sterilized or using suitable birth control * Diagnosis of diabetes (HbA1c \> 6.0) * Diagnosis of diabetic peripheral neuropathy pain in feet * Presence of ongoing diabetic neuropathic for at least 3 months * A pain score of greater than or equal to 4 on the Numerical Pain Rating Scale at screening * Ability to provide written informed consent
Exclusion criteria
* Patients with fibromyalgia or regional pain caused by lumbar or cervical compression * History or diagnosis of significant neurological disease * History and diagnosis of clinically significant psychiatric diseases * Serious liver disease * Poorly controlled diabetes * Hypersensitivity to sodium nitrite or related compounds * Life expectancy \< 6 months * A chronic illness that may increase the risks associated with this study * Active malignancy requiring active anti-neoplastic therapy that will, in the opinion of the investigator, interfere with study treatment or participation * Pregnant or nursing women * Current diagnosis of alcohol or other substance abuse * Current use of sildenafil or other phosphodiesterase Type 5 Inhibitors * History of methemoglobinemia, (met-Hb ≥ 15%) * Subject is involved in litigation or receives worker's compensation * Inability to speak English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reporting of Adverse Events During 12 Week Study Period | 12 weeks | The primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sustained release sodium nitrite compared with placebo over a 12 week treatment period. The following safety parameters will also be assessed: concomitant medication usage, physical examination, vital signs, Comprehensive Metabolic Panel, and complete blood count. Assessment of acute adverse events (i.e., drop in blood pressure, dizziness) after administration of each dose level. Counts are number of subjects reporting at least 1 Adverse Event. The total Adverse Events recorded in each cohort is also reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | 12 weeks | Daily patient reported use of analgesic or medications for neuropathic pain. The use of medications were recorded at the baseline visit and during both the intermediate and final visit for each subject. All subjects used at least one prescription pain medication, other than one subject in the 80-mg dose cohort who used only ibuprofen to control pain. Most subjects used more than one prescription pain medication. There was no change in use of pain medications during the trial period. |
| Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | Baseline (visit 1) and 12 weeks (visit 3) | Subjects completed the Brief pain inventory (BPI), RAND 36 questionnaire, neuropathic pain symptom inventory (NPSI) and Short Form McGill Pain Questionnaire at each visit for these self-reported questionnaires. The BPI is a questionnaire that measures the patient's subjective perception of pain, its exacerbating and alleviating factors, and perceived effect on functional status; the NPSI is a questionnaire that measures the symptoms associated with neuropathic pain; the Short Form McGill Questionnaire subjectively assesses the patients perception of pain described by commonly used adjectives associated with pain. NPSI is average of 12 questions, range from 0 (no pain) to 120 (maximal pain); For BPI severity and interference, questions are scored from 0-10, then there average score for each subsection is calculated (the higher the score, the worse the response); Scores on McGill range from 0-10, lower associated for less pain, then averaged for each sub score and total score. |
| Pharmacokinetics (Blood Levels of Nitrite) | 1 day | Blood levels of nitrite will be assessed for 6 hours post-administration on the initial dosing visit. |
| Assessment of Diabetes. (HbA1C Levels) | 12 weeks | HbA1C levels will be monitored at each visit to determine whether treatment reduces circulating glucose levels. |
| Assessment of Blood Oxygenation. (Pulse Oximetry) | 12 weeks | Pulse oximetry will be used at each visit to determine whether treatment improves oxygen levels in the blood. |
| Clinical Assessment of Pain. (Quantitative Sensory Testing) | 12 weeks | Quantitative sensory testing (QST) was conducted at each visit to determine patients sensitivity to pain. QST was assessed using a quantitative nerve conductance machine where nerves in the distal extremity are subjected to electrical stimulation to determine the sensory threshold of the skin. Nerve conductance measures how fast an electrical impulse moves through the nerve, and nerve velocity measures the speed at which an electrical impulse moves down a neuronal pathway. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo One placebo tablet administered twice daily for 12 weeks.
Placebo: Placebo tablets | 4 |
| 40 mg TV1001sr One 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily.
Sodium nitrite: Sustained release formulation of sodium nitrite | 8 |
| Placebo (2) Two placebo tablets administered twice daily for 12 weeks.
Placebo: Placebo tablets | 5 |
| 80 mg TV1001sr Two 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily.
Sodium nitrite: Sustained release formulation of sodium nitrite | 9 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | 40 mg TV1001sr | Placebo (2) | 80 mg TV1001sr | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 6 Participants | 2 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 5 Participants | 9 Participants | 26 Participants |
| Region of Enrollment United States | 4 participants | 8 participants | 5 participants | 9 participants | 26 participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 1 Participants | 4 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 9 / 9 | 8 / 8 | 7 / 9 |
| serious Total, serious adverse events | 2 / 9 | 2 / 8 | 2 / 8 |
Outcome results
Primary
Reporting of Adverse Events During 12 Week Study Period
The primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sustained release sodium nitrite compared with placebo over a 12 week treatment period. The following safety parameters will also be assessed: concomitant medication usage, physical examination, vital signs, Comprehensive Metabolic Panel, and complete blood count. Assessment of acute adverse events (i.e., drop in blood pressure, dizziness) after administration of each dose level. Counts are number of subjects reporting at least 1 Adverse Event. The total Adverse Events recorded in each cohort is also reported.
Time frame: 12 weeks
Population: Randomized population including dropouts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Placebo | Reporting of Adverse Events During 12 Week Study Period | Subjects reporting at least one Adverse Event | 9 Adverse Events |
| Combined Placebo | Reporting of Adverse Events During 12 Week Study Period | Total Adverse Events reported in each cohort | 29 Adverse Events |
| 40 mg TV1001sr | Reporting of Adverse Events During 12 Week Study Period | Subjects reporting at least one Adverse Event | 8 Adverse Events |
| 40 mg TV1001sr | Reporting of Adverse Events During 12 Week Study Period | Total Adverse Events reported in each cohort | 23 Adverse Events |
| 80 mg TV1001sr | Reporting of Adverse Events During 12 Week Study Period | Subjects reporting at least one Adverse Event | 7 Adverse Events |
| 80 mg TV1001sr | Reporting of Adverse Events During 12 Week Study Period | Total Adverse Events reported in each cohort | 24 Adverse Events |
Secondary
Assessment of Blood Oxygenation. (Pulse Oximetry)
Pulse oximetry will be used at each visit to determine whether treatment improves oxygen levels in the blood.
Time frame: 12 weeks
Population: Oxygen saturation was measured at baseline, V2 and V3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Placebo | Assessment of Blood Oxygenation. (Pulse Oximetry) | V2 | 96.0 % Oxygenation | Standard Deviation 3 |
| Combined Placebo | Assessment of Blood Oxygenation. (Pulse Oximetry) | Baseline | 95.7 % Oxygenation | Standard Deviation 2.6 |
| Combined Placebo | Assessment of Blood Oxygenation. (Pulse Oximetry) | V3 | 94.2 % Oxygenation | Standard Deviation 2.8 |
| 40 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | V2 | 96.4 % Oxygenation | Standard Deviation 2.2 |
| 40 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | Baseline | 95.6 % Oxygenation | Standard Deviation 2.3 |
| 40 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | V3 | 96.0 % Oxygenation | Standard Deviation 2.4 |
| 80 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | Baseline | 96.3 % Oxygenation | Standard Deviation 1.7 |
| 80 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | V3 | 95.1 % Oxygenation | Standard Deviation 2.4 |
| 80 mg TV1001sr | Assessment of Blood Oxygenation. (Pulse Oximetry) | V2 | 95.3 % Oxygenation | Standard Deviation 3.2 |
p-value: 0.93ANOVA
Secondary
Assessment of Diabetes. (HbA1C Levels)
HbA1C levels will be monitored at each visit to determine whether treatment reduces circulating glucose levels.
Time frame: 12 weeks
Population: HbA1c blood levels were analyzed at baseline, V2 and V3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Placebo | Assessment of Diabetes. (HbA1C Levels) | V3 | 7.6 percentage of glycosylated hemoglobin | Standard Deviation 2 |
| Combined Placebo | Assessment of Diabetes. (HbA1C Levels) | V2 | 7.3 percentage of glycosylated hemoglobin | Standard Deviation 1.2 |
| Combined Placebo | Assessment of Diabetes. (HbA1C Levels) | Baseline | 7.7 percentage of glycosylated hemoglobin | Standard Deviation 1.4 |
| 40 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | V3 | 7.7 percentage of glycosylated hemoglobin | Standard Deviation 1.6 |
| 40 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | Baseline | 7.7 percentage of glycosylated hemoglobin | Standard Deviation 1.2 |
| 40 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | V2 | 7.4 percentage of glycosylated hemoglobin | Standard Deviation 0.9 |
| 80 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | V2 | 7.9 percentage of glycosylated hemoglobin | Standard Deviation 1.8 |
| 80 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | Baseline | 8.5 percentage of glycosylated hemoglobin | Standard Deviation 2.4 |
| 80 mg TV1001sr | Assessment of Diabetes. (HbA1C Levels) | V3 | 8.2 percentage of glycosylated hemoglobin | Standard Deviation 1.2 |
p-value: 0.36ANOVA
Secondary
Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires.
Subjects completed the Brief pain inventory (BPI), RAND 36 questionnaire, neuropathic pain symptom inventory (NPSI) and Short Form McGill Pain Questionnaire at each visit for these self-reported questionnaires. The BPI is a questionnaire that measures the patient's subjective perception of pain, its exacerbating and alleviating factors, and perceived effect on functional status; the NPSI is a questionnaire that measures the symptoms associated with neuropathic pain; the Short Form McGill Questionnaire subjectively assesses the patients perception of pain described by commonly used adjectives associated with pain. NPSI is average of 12 questions, range from 0 (no pain) to 120 (maximal pain); For BPI severity and interference, questions are scored from 0-10, then there average score for each subsection is calculated (the higher the score, the worse the response); Scores on McGill range from 0-10, lower associated for less pain, then averaged for each sub score and total score.
Time frame: Baseline (visit 1) and 12 weeks (visit 3)
Population: NPS is a sum of total scores, McGill and BPI an average of the scores for each question.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V1 | 5.1 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V1 | 6.0 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V3 | 3.6 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V3 | 4.3 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V3 | 3.2 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V1 | 5.0 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V1 | 5.0 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V3 | 43.4 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V1 | 5.1 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V3 | 4.8 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V1 | 47.4 units on a scale |
| Combined Placebo | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V3 | 4.1 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V3 | 4.2 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V1 | 4.3 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V1 | 34.7 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V1 | 3.9 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V3 | 30.0 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V3 | 2.5 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V1 | 3.7 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V3 | 1.9 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V1 | 4.6 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V3 | 2.8 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V3 | 3.8 units on a scale |
| 40 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V1 | 4.4 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V3 | 5.7 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V1 | 5.9 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V3 | 46.0 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Interferrence-V1 | 6.4 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Intermittent-V3 | 5.3 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V1 | 5.9 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | BPI: Severity Score-V3 | 5.1 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V1 | 4.4 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V3 | 4.6 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | NPSI: Total-V1 | 56.0 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Continuous-V3 | 4.3 units on a scale |
| 80 mg TV1001sr | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | McGill: Total-V1 | 4.8 units on a scale |
p-value: 0.05ANOVA
Secondary
Clinical Assessment of Pain. (Quantitative Sensory Testing)
Quantitative sensory testing (QST) was conducted at each visit to determine patients sensitivity to pain. QST was assessed using a quantitative nerve conductance machine where nerves in the distal extremity are subjected to electrical stimulation to determine the sensory threshold of the skin. Nerve conductance measures how fast an electrical impulse moves through the nerve, and nerve velocity measures the speed at which an electrical impulse moves down a neuronal pathway.
Time frame: 12 weeks
Population: Analyzed only the subjects that completed testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: Baseline | 3.9 meters per second | Standard Deviation 1.4 |
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V2 | 4.3 meters per second | Standard Deviation 1.8 |
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V3 | 3.5 meters per second | Standard Deviation 1.2 |
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: Baseline | 44.7 meters per second | Standard Deviation 6.5 |
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V2 | 40.1 meters per second | Standard Deviation 5.3 |
| Combined Placebo | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V3 | 43.2 meters per second | Standard Deviation 6.4 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V3 | 37.7 meters per second | Standard Deviation 3.2 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: Baseline | 3.4 meters per second | Standard Deviation 0.7 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: Baseline | 41.1 meters per second | Standard Deviation 4.3 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V2 | 39.3 meters per second | Standard Deviation 7.8 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V2 | 3.1 meters per second | Standard Deviation 0.9 |
| 40 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V3 | 3.2 meters per second | Standard Deviation 0.6 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V2 | 5.2 meters per second | Standard Deviation 3 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: V3 | 4.2 meters per second | Standard Deviation 1.5 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V3 | 46.8 meters per second | Standard Deviation 4.2 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: Baseline | 39.4 meters per second | Standard Deviation 8.2 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Conductance: Baseline | 6.0 meters per second | Standard Deviation 2.9 |
| 80 mg TV1001sr | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Nerve Velocity: V2 | 42.3 meters per second | Standard Deviation 10.7 |
p-value: 0.15ANOVA
Secondary
Pharmacokinetics (Blood Levels of Nitrite)
Blood levels of nitrite will be assessed for 6 hours post-administration on the initial dosing visit.
Time frame: 1 day
Population: All subjects who were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Placebo | Pharmacokinetics (Blood Levels of Nitrite) | 1399 ng/ml | Standard Deviation 47 |
| 40 mg TV1001sr | Pharmacokinetics (Blood Levels of Nitrite) | 9699 ng/ml | Standard Deviation 10199 |
| 80 mg TV1001sr | Pharmacokinetics (Blood Levels of Nitrite) | 9905 ng/ml | Standard Deviation 12383 |
Secondary
The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain.
Daily patient reported use of analgesic or medications for neuropathic pain. The use of medications were recorded at the baseline visit and during both the intermediate and final visit for each subject. All subjects used at least one prescription pain medication, other than one subject in the 80-mg dose cohort who used only ibuprofen to control pain. Most subjects used more than one prescription pain medication. There was no change in use of pain medications during the trial period.
Time frame: 12 weeks
Population: Analyzed only those subjects who completed 12 weeks of testing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using any medicine to treat pain | 9 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Gabapentin | 6 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Lyrica | 4 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Morphine | 2 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Tramadol | 1 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Cymbalta | 1 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Flexeril | 1 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Naproxen | 1 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Percocet | 3 Participants |
| Combined Placebo | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Vicodin | 2 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Percocet | 1 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using any medicine to treat pain | 7 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Cymbalta | 1 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Tramadol | 3 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Gabapentin | 6 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Vicodin | 2 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Naproxen | 3 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Lyrica | 4 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Flexeril | 0 Participants |
| 40 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Morphine | 1 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Naproxen | 0 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Morphine | 0 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Tramadol | 3 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Cymbalta | 2 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Percocet | 0 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Flexeril | 2 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using any medicine to treat pain | 8 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Vicodin | 1 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Gabapentin | 3 Participants |
| 80 mg TV1001sr | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Subjects using Lyrica | 4 Participants |