Back to resultsTopically Applied Bisphosphocin Nu-3 on Infected Diabetic Ulcers of Subjects With Type I or II Diabetes Mellitus
Primary Purpose
Diabetic Foot Infections
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bisphosphocin Nu-3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Foot Infections
Eligibility Criteria
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investigation-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care.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:
- Surgically sterile with bilateral tubal ligation or hysterectomy.
- Post-menopausal for at least one year.
- 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.
- Subjects willing to undergo pre-and post-clinical investigation blood collection, physical exams and laboratory investigations.
Exclusion Criteria:
- A DUSS Score above 3.
- DUSS Probing to Bone = "Yes"
- An ulcer area(s) greater than 6 cm2 or more than two (2) ulcers
- Any subject that has received systemic or topical antibiotics within the last seven (7) days
- Any subject on topical antimicrobial treatment for their infected diabetic foot ulcer whose ulcer is responding to treatment
- Any subject that would be unable to follow the protocol procedures, safely monitor the infection status at home, and return for schedule visits
- Positive pregnancy test at Screening or Visit 2
- Active infection as demonstrated by temperature > 37.5 oC and clinical features of active infection.
- Known immunosuppression or taking immunosuppressive agents including systemic steroids.
- History of severe co-morbidity with expected patient survival ≤ 6 months.
- Pregnancy or lactation
- Intake of investigational drugs within 28 days prior to enrollment.
- History of concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.
- Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
- Unwillingness or language barrier precluding adequate understanding of the trial procedure or cooperation with trial site personnel.
- Known or suspected active abuse of alcohol, narcotics or non-prescription drugs.
- Other planned surgical procedures within 30 days prior to or 30 days post-index procedure.
- Prior enrollment in this clinical trial
Sites / Locations
- Center for Clinical Research, Inc.
- Journey Research, Inc.
- Clinical Research Solutions
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Bisphosphocin Nu-3
Placebo
Arm Description
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
Dosage Form: Diluent, Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02737722
Brief Title
Topically Applied Bisphosphocin Nu-3 on Infected Diabetic Ulcers of Subjects With Type I or II Diabetes Mellitus
Official Title
A Phase I/IIa, Randomized Double Blind, Placebo-Controlled, Dose Escalating Study to Evaluate the Safety and Tolerability of Topically Applied Bisphosphocin Nu-3 on Infected Diabetic Ulcers of Subjects With Type I or II Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
April 2016 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
February 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lakewood-Amedex Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bisphosphocin Nu-3
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Dosage Form: Diluent, Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days
Intervention Type
Drug
Intervention Name(s)
Bisphosphocin Nu-3
Other Intervention Name(s)
Nu-3
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE)
Description
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)
Title
Number of Participants With Normal and Abnormal Cultures at Visits 2, 3, 4, and 5
Description
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)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS)
Description
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)
Title
Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score
Description
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)
Title
Mean Change From Baseline in Ulcer Area in the ITT Population
Description
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)
Title
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population
Description
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)
Title
Mean Change From Baseline in Ulcer Area in the Per-Protocol Population
Description
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)
Title
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Surgically sterile with bilateral tubal ligation or hysterectomy.
Post-menopausal for at least one year.
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.
Subjects willing to undergo pre-and post-clinical investigation blood collection, physical exams and laboratory investigations.
Exclusion Criteria:
A DUSS Score above 3.
DUSS Probing to Bone = "Yes"
An ulcer area(s) greater than 6 cm2 or more than two (2) ulcers
Any subject that has received systemic or topical antibiotics within the last seven (7) days
Any subject on topical antimicrobial treatment for their infected diabetic foot ulcer whose ulcer is responding to treatment
Any subject that would be unable to follow the protocol procedures, safely monitor the infection status at home, and return for schedule visits
Positive pregnancy test at Screening or Visit 2
Active infection as demonstrated by temperature > 37.5 oC and clinical features of active infection.
Known immunosuppression or taking immunosuppressive agents including systemic steroids.
History of severe co-morbidity with expected patient survival ≤ 6 months.
Pregnancy or lactation
Intake of investigational drugs within 28 days prior to enrollment.
History of concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.
Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
Unwillingness or language barrier precluding adequate understanding of the trial procedure or cooperation with trial site personnel.
Known or suspected active abuse of alcohol, narcotics or non-prescription drugs.
Other planned surgical procedures within 30 days prior to or 30 days post-index procedure.
Prior enrollment in this clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Kates, PhD
Organizational Affiliation
Lakewood-Amedex Inc
Official's Role
Study Director
Facility Information:
Facility Name
Center for Clinical Research, Inc.
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Journey Research, Inc.
City
Oldsmar
State/Province
Florida
ZIP/Postal Code
34677
Country
United States
Facility Name
Clinical Research Solutions
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37067
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Topically Applied Bisphosphocin Nu-3 on Infected Diabetic Ulcers of Subjects With Type I or II Diabetes Mellitus
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