Diabetic Foot Infections
Conditions
Brief summary
Phase I/IIa, five cohort ascending dose with two dosing arms per cohort, study in Type I or II diabetes mellitus subjects with a chronic infected diabetic ulcer defined as having a DUSS score of 0 to 3 and DFI wound score of 1 to 3.
Detailed description
The study is designed to run the cohorts in series with the completion of the first cohort before initiating the next dosing level. At all study visits the ulcer will be visually examined for any changes and photographed using the Aranz Medical Silhouette™ system that will calculate area and depth of the ulcer. In Arm 1, eligible subjects will be treated with a single application of Nu-3 or placebo in 4 to 1 ratio to judge the initial safety of Nu-3 over a brief one (1) hour interval and 24-hr interval post application. Bisphosphocin Nu-3 will be applied topically to the chronic infected ulcer, covered with a non-abrasive bandage following the initial observation period. The subject will be released with verbal instructions to leave the bandage on the wound and return for a follow up visit within 24h ± 2h. At the follow up visit, the bandage will be removed, the ulcer visually examined and the subject cleared for the MAD Arm 2 based on the recommendation of the PI and absence of any SAEs. In Arm 2, eligible subjects which are those who have been approved by the PI after the Visit 2 examination will be instructed in the proper application of bisphosphocin Nu-3. The subjects will be observed applying the first dose in the clinic to ensure compliance. Subjects will then be given a 7 day supply and sent home to continue treatment. Visit 4 or earlier in the case of any adverse events, subjects will return to the clinic for an examination, including visual examination of the ulcer, vital signs, adverse events, photo documentation, collection of a sample for microbiology and concomitant medication use. A final follow up visit will be scheduled +7 days after last dose of study medication (Day 15) for a complete examination as described above.
Interventions
DRUGBisphosphocin Nu-3
DRUGPlacebo
Sponsors
Lakewood-Amedex Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women between the ages of 18 and 85. 2. Voluntary written consent, given before performance of any clinical investigation-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care. 3. Non-hospitalized ambulatory subjects suffering from Diabetes mellitus, Type I or II 4. Diabetic foot ulcer(s) with a DUSS Score of 0 to 3 5. Ulcerated area(s) of not more than two (2) ulcers between 0.5 to 6 cm2 6. Any female of child bearing age must consent to use medically acceptable birth control for the duration of the study 7. Female subjects must meet at least one of the following additional criteria: 1. Surgically sterile with bilateral tubal ligation or hysterectomy. 2. Post-menopausal for at least one year. 3. If of child-bearing potential, practicing an acceptable method of birth control for the duration of the clinical investigation as judged by the Investigator, such as condoms, foams, jellies, diaphragm, intrauterine device or abstinence. 8. Subjects willing to undergo pre-and post-clinical investigation blood collection, physical exams and laboratory investigations.
Exclusion criteria
1. A DUSS Score above 3. 2. DUSS Probing to Bone = Yes 3. An ulcer area(s) greater than 6 cm2 or more than two (2) ulcers 4. Any subject that has received systemic or topical antibiotics within the last seven (7) days 5. Any subject on topical antimicrobial treatment for their infected diabetic foot ulcer whose ulcer is responding to treatment 6. Any subject that would be unable to follow the protocol procedures, safely monitor the infection status at home, and return for schedule visits 7. Positive pregnancy test at Screening or Visit 2 8. Active infection as demonstrated by temperature \> 37.5 oC and clinical features of active infection. 9. Known immunosuppression or taking immunosuppressive agents including systemic steroids. 10. History of severe co-morbidity with expected patient survival ≤ 6 months. 11. Pregnancy or lactation 12. Intake of investigational drugs within 28 days prior to enrollment. 13. History of concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol. 14. Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel. 15. Unwillingness or language barrier precluding adequate understanding of the trial procedure or cooperation with trial site personnel. 16. Known or suspected active abuse of alcohol, narcotics or non-prescription drugs. 17. Other planned surgical procedures within 30 days prior to or 30 days post-index procedure. 18. Prior enrollment in this clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) | up to Day 15 (Visit 5) | The severity of each adverse event, as judged by the investigator, was graded according to the CTCAE v4.02. Treatment-emergent adverse events are defined as adverse events with onset times after dosing, or pre-existing adverse events that worsened during the study. |
| Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Days 1, 2, 9, and 15 (Visits 2, 3, 4, and 5, respectively) | The microbiological response to bisphosphocin Nu-3 based on aerobic and anaerobic culture and sensitivity was determined by measuring the reduction of pathogenic bacteria following Nu-3 treatment. Each laboratory used their own standards to decide whether the cultures were normal or abnormal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Ulcer Area in the ITT Population | Baseline; Day 15 (Visit 5) | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis. |
| Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population | Baseline; Day 15 (Visit 5) | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis. |
| Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS) | Baseline and Day 15 (Visit 5) | Clinical response to bisphosphocin Nu-3 was determined by visual evaluation of ulcers, based on the Principal Investigator's judgement, following Nu-3 treatment. Ulcers were scored based on the DUSS. The following 4 parameters were scored as either 0 or 1. Palpable pedal pulses: presence, 0; absence, 1. Probing to the bone: no, 0; yes, 1. Location of ulcer: toe, 0; foot, 1. Number of ulcerations: single, 0; multiple, 1. The four parameter scores were summed to calculate a total score ranging from 0 to 4, with a higher score indicating increased severity. Baseline is defined as the last non-missing value obtained prior to receiving study drug. Change from Baseline is calculated as the post-Baseline value minus the Baseline value. |
| Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population | Baseline; Day 15 (Visit 5) | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis. |
| Mean Change From Baseline in Ulcer Area in the Per-Protocol Population | Baseline; Day 15 (Visit 5) | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis. |
| Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score | Baseline; Day 15 (Visit 5) | Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. The Diabetic Foot Ulcer Wound Infection Score is a numerical scoring system comprised of 7 wound parameters. The score for each individual parameter is summed to calculate a total score, ranging from 0 (less severe infection) to 19 (more severe infection). Parameters are as follows: purulent discharge (0, absent; 3, present); non-purulent discharge (serious, sanguineous) (0, absent; 1, mild); other signs and symptoms of inflammation (erythema, induration, tenderness, pain; 0, none; 1, mild; 2, moderate; 3, severe); local warmth (relative to uninfected contralateral foot) (0, same; 1, mildly increased; 2, moderately increased; 3, severely increased). |
Countries
United States
Participant flow
Pre-assignment details
Overall, 48 participants were screened; 17 were screen failures and weren't enrolled. One participant was enrolled but not randomized.
Participants by arm
| Arm | Count |
|---|---|
| 0.1% Bisphosphocin Nu-3 Participants received a single topical administration of 0.1% Nu-3 solution in saline on Day 1. Participants then applied the same dose twice a day for 7 days. | 8 |
| 1% Bisphosphocin Nu-3 Participants received a single topical administration of 1% Nu-3 solution in saline on Day 1. Participants then applied the same dose twice a day for 7 days. | 8 |
| 2% Bisphosphocin Nu-3 Participants received a single topical administration of 2% Nu-3 solution in saline on Day 1. Participants then applied the same dose twice a day for 7 days. | 8 |
| Placebo Participants received a single topical administration of matching placebo on Day 1. Participants then applied the same dose twice a day for 7 days. | 6 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | 2% Bisphosphocin Nu-3 | 1% Bisphosphocin Nu-3 | 0.1% Bisphosphocin Nu-3 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 6.54 | 60.5 years STANDARD_DEVIATION 14.03 | 59.3 years STANDARD_DEVIATION 8.41 | 55.6 years STANDARD_DEVIATION 8.21 | 59.0 years STANDARD_DEVIATION 9.64 |
| Mean Diabetic Foot Ulcer Wound Infection Score | 4.33 units on a scale STANDARD_DEVIATION 1.31 | 4.63 units on a scale STANDARD_DEVIATION 1.69 | 4.50 units on a scale STANDARD_DEVIATION 1.6 | 4.38 units on a scale STANDARD_DEVIATION 0.92 | 4.47 units on a scale STANDARD_DEVIATION 1.31 |
| Mean Diabetic Ulcer Wound Scoring System (DUSS) Score | 1.00 units on a scale STANDARD_DEVIATION 0.89 | 1.13 units on a scale STANDARD_DEVIATION 0.64 | 1.25 units on a scale STANDARD_DEVIATION 0.71 | 1.13 units on a scale STANDARD_DEVIATION 0.35 | 1.13 units on a scale STANDARD_DEVIATION 0.63 |
| Mean Ulcer Area in the Intent-to-Treat Population | 0.8 centimeters squared (cm^2) STANDARD_DEVIATION 0.2 | 1.9 centimeters squared (cm^2) STANDARD_DEVIATION 1.25 | 1.8 centimeters squared (cm^2) STANDARD_DEVIATION 1.54 | 1.5 centimeters squared (cm^2) STANDARD_DEVIATION 1.23 | 1.5 centimeters squared (cm^2) STANDARD_DEVIATION 1.22 |
| Mean Ulcer Area in the Per-Protocol Population | 0.8 cm^2 STANDARD_DEVIATION 0.2 | 1.9 cm^2 STANDARD_DEVIATION 1.25 | 1.8 cm^2 STANDARD_DEVIATION 1.54 | 1.7 cm^2 STANDARD_DEVIATION 1.36 | 1.6 cm^2 STANDARD_DEVIATION 1.24 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown or Missing | 3 Participants | 0 Participants | 0 Participants | 8 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 7 Participants | 7 Participants | 0 Participants | 17 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 5 Participants | 7 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 1 / 8 | 0 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 1 / 8 | 0 / 6 |
Outcome results
Primary
Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5
The microbiological response to bisphosphocin Nu-3 based on aerobic and anaerobic culture and sensitivity was determined by measuring the reduction of pathogenic bacteria following Nu-3 treatment. Each laboratory used their own standards to decide whether the cultures were normal or abnormal.
Time frame: Days 1, 2, 9, and 15 (Visits 2, 3, 4, and 5, respectively)
Population: Intent-to-Treat (ITT) Population: all randomized participants. Only those participants with available data were analyzed. Microbiology results were not collected in the database for participants in the 0.1% cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Abnormal Culture | 7 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Normal Culture | 1 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Normal Culture | 1 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Abnormal Culture | 6 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Abnormal Culture | 6 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Normal Culture | 2 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Normal Culture | 1 participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Abnormal Culture | 7 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Abnormal Culture | 6 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Normal Culture | 0 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Abnormal Culture | 7 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Normal Culture | 0 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Normal Culture | 2 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Abnormal Culture | 7 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Abnormal Culture | 7 participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Normal Culture | 0 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Abnormal Culture | 3 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Normal Culture | 0 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 1 (Visit 2), Abnormal Culture | 4 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Abnormal Culture | 3 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 2 (Visit 3), Normal Culture | 1 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Normal Culture | 0 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 9 (Visit 4), Abnormal Culture | 2 participants |
| Placebo | Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5 | Day 15 (Visit 5), Normal Culture | 1 participants |
Comparison: Day 1 (Visit 2)p-value: 0.5152Fisher Exact
Comparison: Day 1 (Visit 2)p-value: 1Fisher Exact
Comparison: Day 2 (Visit 3)p-value: 1Fisher Exact
Comparison: Day 2 (Visit 3)p-value: 1Fisher Exact
Comparison: Day 9 (Visit 4)p-value: 1Fisher Exact
Comparison: Day 9 (Visit 4)p-value: 1Fisher Exact
Comparison: Day 15 (Visit 5)p-value: 1Fisher Exact
Comparison: Day 15 (Visit 5)p-value: 0.3636Fisher Exact
Primary
Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE)
The severity of each adverse event, as judged by the investigator, was graded according to the CTCAE v4.02. Treatment-emergent adverse events are defined as adverse events with onset times after dosing, or pre-existing adverse events that worsened during the study.
Time frame: up to Day 15 (Visit 5)
Population: Safety Population: all participants administered any amount of investigational product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) | 0 Participants |
| 1% Bisphosphocin Nu-3 | Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) | 0 Participants |
| 2% Bisphosphocin Nu-3 | Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) | 0 Participants |
| Placebo | Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) | 0 Participants |
Secondary
Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. The Diabetic Foot Ulcer Wound Infection Score is a numerical scoring system comprised of 7 wound parameters. The score for each individual parameter is summed to calculate a total score, ranging from 0 (less severe infection) to 19 (more severe infection). Parameters are as follows: purulent discharge (0, absent; 3, present); non-purulent discharge (serious, sanguineous) (0, absent; 1, mild); other signs and symptoms of inflammation (erythema, induration, tenderness, pain; 0, none; 1, mild; 2, moderate; 3, severe); local warmth (relative to uninfected contralateral foot) (0, same; 1, mildly increased; 2, moderately increased; 3, severely increased).
Time frame: Baseline; Day 15 (Visit 5)
Population: ITT Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score | -2.38 score on a scale | Standard Deviation 1.41 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score | -1.50 score on a scale | Standard Deviation 3.42 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score | -2.86 score on a scale | Standard Deviation 1.57 |
| Placebo | Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score | -3.00 score on a scale | Standard Deviation 2.1 |
p-value: 0.432Wilcoxon Rank Sum Test
p-value: 0.435Wilcoxon Rank Sum Test
p-value: 0.715Wilcoxon Rank Sum Test
Secondary
Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS)
Clinical response to bisphosphocin Nu-3 was determined by visual evaluation of ulcers, based on the Principal Investigator's judgement, following Nu-3 treatment. Ulcers were scored based on the DUSS. The following 4 parameters were scored as either 0 or 1. Palpable pedal pulses: presence, 0; absence, 1. Probing to the bone: no, 0; yes, 1. Location of ulcer: toe, 0; foot, 1. Number of ulcerations: single, 0; multiple, 1. The four parameter scores were summed to calculate a total score ranging from 0 to 4, with a higher score indicating increased severity. Baseline is defined as the last non-missing value obtained prior to receiving study drug. Change from Baseline is calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Day 15 (Visit 5)
Population: ITT Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS) | 0.13 score on a scale | Standard Deviation 0.64 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS) | -0.13 score on a scale | Standard Deviation 0.35 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS) | -0.14 score on a scale | Standard Deviation 0.69 |
| Placebo | Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS) | -0.33 score on a scale | Standard Deviation 0.52 |
p-value: 0.172Wilcoxon Rank Sum Test
p-value: 0.365Wilcoxon Rank Sum Test
p-value: 0.619Wilcoxon Rank Sum Test
Secondary
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis.
Time frame: Baseline; Day 15 (Visit 5)
Population: ITT Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population | 25.2 percentage of area | Standard Deviation 34.41 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population | 10.8 percentage of area | Standard Deviation 51.94 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population | 54.0 percentage of area | Standard Deviation 36.67 |
| Placebo | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population | 41.0 percentage of area | Standard Deviation 41.56 |
p-value: 0.464Wilcoxon Rank Sum Test
p-value: 0.464Wilcoxon Rank Sum Test
p-value: 0.465Wilcoxon Rank Sum Test
Secondary
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis.
Time frame: Baseline; Day 15 (Visit 5)
Population: Per-Protocol Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population | 22.4 percentage of area | Standard Deviation 39.77 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population | 10.8 percentage of area | Standard Deviation 51.94 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population | 54.0 percentage of area | Standard Deviation 36.67 |
| Placebo | Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population | 41.0 percentage of area | Standard Deviation 41.56 |
p-value: 0.465Wilcoxon Rank Sum Test
p-value: 0.464Wilcoxon Rank Sum Test
p-value: 0.465Wilcoxon Rank Sum Test
Secondary
Mean Change From Baseline in Ulcer Area in the ITT Population
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis.
Time frame: Baseline; Day 15 (Visit 5)
Population: ITT Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the ITT Population | -0.3 centimeters squared (cm^2) | Standard Deviation 0.62 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the ITT Population | -0.2 centimeters squared (cm^2) | Standard Deviation 0.77 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the ITT Population | -0.7 centimeters squared (cm^2) | Standard Deviation 0.68 |
| Placebo | Mean Change From Baseline in Ulcer Area in the ITT Population | -0.3 centimeters squared (cm^2) | Standard Deviation 0.32 |
p-value: 0.519Wilcoxon Rank Sum Test
p-value: 0.519Wilcoxon Rank Sum Test
p-value: 0.153Wilcoxon Rank Sum Test
Secondary
Mean Change From Baseline in Ulcer Area in the Per-Protocol Population
Change from Baseline is calculated as the post-Baseline value minus the Baseline value. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis.
Time frame: Baseline; Day 15 (Visit 5)
Population: Per-Protocol Population: all participants who met enrollment criteria, received all doses of investigational product as required by the protocol, and had no major protocol violations. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the Per-Protocol Population | -0.1 centimeters squared (cm^2) | Standard Deviation 0.37 |
| 1% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the Per-Protocol Population | -0.2 centimeters squared (cm^2) | Standard Deviation 0.77 |
| 2% Bisphosphocin Nu-3 | Mean Change From Baseline in Ulcer Area in the Per-Protocol Population | -0.7 centimeters squared (cm^2) | Standard Deviation 0.68 |
| Placebo | Mean Change From Baseline in Ulcer Area in the Per-Protocol Population | -0.3 centimeters squared (cm^2) | Standard Deviation 0.32 |
p-value: 0.361Wilcoxon Rank Sum Test
p-value: 0.519Wilcoxon Rank Sum Test
p-value: 0.153Wilcoxon Rank Sum Test
Post Hoc
Median Percent Change From Baseline in the Percentage Area Reduction for Ulcers in the Per-Protocol Population
Percent change from Baseline is calculated as the \[(post-Baseline value minus the Baseline value)/Baseline value\] x 100. Baseline is defined as the last non-missing value obtained prior to receiving study drug. For participants who have more than one ulcer, the measurement of all ulcers were combined for analysis.
Time frame: Baseline; Day 15 (Visit 5)
Population: Per-Protocol Population. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.1% Bisphosphocin Nu-3 | Median Percent Change From Baseline in the Percentage Area Reduction for Ulcers in the Per-Protocol Population | 4.6 percent change |
| 1% Bisphosphocin Nu-3 | Median Percent Change From Baseline in the Percentage Area Reduction for Ulcers in the Per-Protocol Population | 13.1 percent change |
| 2% Bisphosphocin Nu-3 | Median Percent Change From Baseline in the Percentage Area Reduction for Ulcers in the Per-Protocol Population | 65.6 percent change |
| Placebo | Median Percent Change From Baseline in the Percentage Area Reduction for Ulcers in the Per-Protocol Population | 29.9 percent change |
p-value: 0.465Wilcoxon Rank Sum Test
p-value: 0.464Wilcoxon Rank Sum Test
p-value: 0.465Wilcoxon Rank Sum Test
Post Hoc
Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response
Global impression of microbiological response was conducted by comparing culture value from Baseline to Visit 5 (Day 15). If culture values were not reported by the local laboratory, numerical values were assigned using the following criteria: heavy growth, 4+, moderate growth, 2+, scant, 1+, no bacteria, 0.
Time frame: Baseline; Day 15 (Visit 5)
Population: Per-Protocol Population. Microbiology results were not collected in the database for participants in the 0.1% cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1% Bisphosphocin Nu-3 | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | No apparent effect (negative) | 62 percentage of participants |
| 1% Bisphosphocin Nu-3 | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | Apparent effect (positive) | 38 percentage of participants |
| 2% Bisphosphocin Nu-3 | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | No apparent effect (negative) | 38 percentage of participants |
| 2% Bisphosphocin Nu-3 | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | Apparent effect (positive) | 62 percentage of participants |
| Placebo | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | No apparent effect (negative) | 75 percentage of participants |
| Placebo | Percentage of Participants With a Positive and Negative Global Clinical Impression of Microbiology Response | Apparent effect (positive) | 25 percentage of participants |