Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bisphosphocin Nu-3 | Experimental | Dosage Form: Topical Antimicrobial, Dosage: 1mg/mL, 10 mg/mL, 20 mg/mL, 50 mg/mL, 100 mg/mL Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days |
|
| Placebo | Placebo Comparator | Dosage Form: Diluent, Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bisphosphocin Nu-3 | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to Day 15 (Visit 5) |
| 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. | Days 1, 2, 9, and 15 (Visits 2, 3, 4, and 5, respectively) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Men and women between the ages of 18 and 85.
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.
Non-hospitalized ambulatory subjects suffering from Diabetes mellitus, Type I or II
Diabetic foot ulcer(s) with a DUSS Score of 0 to 3
Ulcerated area(s) of not more than two (2) ulcers between 0.5 to 6 cm2
Any female of child bearing age must consent to use medically acceptable birth control for the duration of the study
Female subjects must meet at least one of the following additional criteria:
Subjects willing to undergo pre-and post-clinical investigation blood collection, physical exams and laboratory investigations.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Steve Kates, PhD | Lakewood-Amedex Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Clinical Research, Inc. | San Francisco | California | 94115 | United States | ||
| Journey Research, Inc. |
Not provided
Not provided
Not provided
Not provided
Not provided
Overall, 48 participants were screened; 17 were screen failures and weren't enrolled. One participant was enrolled but not randomized.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 1% Bisphosphocin Nu-3 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Population: all participants administered any amount of investigational product | Posted | Count of Participants | Participants | up to Day 15 (Visit 5) |
|
up to Day 15 (Visit 5)
Treatment-emergent adverse events, defined as adverse events with onset times after dosing, or pre-existing adverse events that worsened during the study, are reported.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Streptococcal bacteraemia | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 14.1 | Non-systematic Assessment |
Participants were enrolled into Cohorts 1, 2, and 3; Cohorts 4 and 5 were not enrolled because of challenges with enrolling participants. Additionally, Lakewood Amedex developed a gel formulation to be used for subsequent clinical studies.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Lakewood Amedex | 941 928 7774 | poconnor@lakewoodamedex.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 15, 2016 | Jul 2, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 31, 2017 | Jul 2, 2019 | SAP_001.pdf |
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| Baseline and Day 15 (Visit 5) |
| 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). | Baseline; Day 15 (Visit 5) |
| 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. | Baseline; Day 15 (Visit 5) |
| 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. | Baseline; Day 15 (Visit 5) |
| 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. | Baseline; Day 15 (Visit 5) |
| 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. | Baseline; Day 15 (Visit 5) |
| Oldsmar |
| Florida |
| 34677 |
| United States |
| Clinical Research Solutions | Franklin | Tennessee | 37067 | United States |
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.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Mean Diabetic Ulcer Wound Scoring System (DUSS) Score | 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. Data are collected in the Intent-to-Treat Population, comprised of all randomized participants. | Mean | Standard Deviation | units on a scale |
|
| Mean Diabetic Foot Ulcer Wound Infection Score | Baseline is defined as the last non-missing value obtained prior to receiving study drug. The score for each parameter is summed to calculate a total score, from 0 (less severe infection) to 19 (more severe infection). Parameters: purulent discharge (0, absent; 3, present); non-purulent discharge (serious, sanguineous) (0, absent; 1, mild); other signs/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). | Mean | Standard Deviation | units on a scale |
|
| Mean Ulcer Area in the Intent-to-Treat Population | Baseline is defined as the last non-missing value obtained prior to receiving study drug. | Mean | Standard Deviation | centimeters squared (cm^2) |
|
| Mean Ulcer Area in the Per-Protocol Population | Data were collected in the Per-Protocol Population, comprised of all participants who met enrollment criteria, received all doses of investigational product as required by the protocol, and had no major protocol violations. | Mean | Standard Deviation | cm^2 |
|
| OG001 |
| 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
| 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. | 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. | Posted | Number | participants | Days 1, 2, 9, and 15 (Visits 2, 3, 4, and 5, respectively) |
|
|
|
|
| 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. | ITT Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 15 (Visit 5) |
|
|
|
|
| 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). | ITT Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 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. | ITT Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | centimeters squared (cm^2) | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 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. | ITT Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | percentage of area | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | centimeters squared (cm^2) | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 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. | Per-Protocol Population. Only those participants with available data were analyzed. | Posted | Mean | Standard Deviation | percentage of area | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 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. | Per-Protocol Population. Microbiology results were not collected in the database for participants in the 0.1% cohort. | Posted | Number | percentage of participants | Baseline; Day 15 (Visit 5) |
|
|
|
| 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. | Per-Protocol Population. Only those participants with available data were analyzed. | Posted | Median | Full Range | percent change | Baseline; Day 15 (Visit 5) |
|
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | 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. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | 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. | 0 | 8 | 1 | 8 | 1 | 8 |
| EG003 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
Not provided
Not provided
| Male |
|
|
|
|
| Day 1 (Visit 2), Abnormal Culture |
|
|
| Day 2 (Visit 3), Normal Culture |
|
|
| Day 2 (Visit 3), Abnormal Culture |
|
|
| Day 9 (Visit 4), Normal Culture |
|
|
| Day 9 (Visit 4), Abnormal Culture |
|
|
| Day 15 (Visit 5), Normal Culture |
|
|
| Day 15 (Visit 5), Abnormal Culture |
|
|
| 1.0000 |
| Superiority |
| Day 2 (Visit 3) | Fisher Exact | 1.0000 | Superiority |
| Day 2 (Visit 3) | Fisher Exact | 1.0000 | Superiority |
| Day 9 (Visit 4) | Fisher Exact | 1.0000 | Superiority |
| Day 9 (Visit 4) | Fisher Exact | 1.0000 | Superiority |
| Day 15 (Visit 5) | Fisher Exact | 1.0000 | Superiority |
| Day 15 (Visit 5) | Fisher Exact | 0.3636 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.619 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.715 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.153 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.465 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.153 | Superiority |
| Superiority |
| Wilcoxon Rank Sum Test | 0.465 | Superiority |
|
| Superiority |
| Wilcoxon Rank Sum Test | 0.465 | Superiority |