Diabetic Foot InfectionsPhase 1/2NCT02737722
Topically Applied Bisphosphocin Nu-3 on Infected Diabetic Ulcers of Subjects With Type I or II Diabetes Mellitus
A Phase 1/2 study testing Bisphosphocin Nu-3 in people with Diabetic Foot Infections, run by Lakewood-Amedex Inc at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetic Foot Infections
- What is being tested?
- Bisphosphocin Nu-3
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2016to Feb 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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investigation-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care.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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Clinical Research Solutions
Franklin, Tennessee, 37067
Journey Research, Inc.
Oldsmar, Florida, 34677
Center for Clinical Research, Inc.
San Francisco, California, 94115
About this study
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
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.
Read the 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.
- Conditions
- Diabetic Foot Infections
- Being tested
- Bisphosphocin Nu-3, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bisphosphocin Nu-3Drug
Also called Nu-3
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Bisphosphocin Nu-3 |
| Placebo | Placebo comparator | Dosage Form: Diluent, Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Days 1, 2, 9, and 15 (Visits 2, 3, 4, and 5, respectively)
Secondary outcomes (6)
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline; Day 15 (Visit 5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionAug 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic Foot InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lakewood-Amedex Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steve Kates, PhD, Study director, Lakewood-Amedex Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02737722
- Sponsor's protocol ID
- LAI2014-1
- Status last verified
- Oct 2019
- First submitted
- 5 Apr 2016
- Last updated
- 19 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02737722
- Acronym / sponsor ID
- LAI2014-1
- Conditions
- Diabetic Foot Infections
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Lakewood-Amedex IncIndustry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 14 Apr 2016 (estimated)
- Results
- Posted 19 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bisphosphocin Nu-3 | Experimental | Drug: Bisphosphocin Nu-3Dosage 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 | Drug: PlaceboDosage Form: Diluent, Frequency: QD for day 1, 2x daily for 7 days, Duration: 8 days |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bisphosphocin Nu-3Also: Nu-3 | Drug | Bisphosphocin Nu-3 |
| Placebo | Drug | Placebo |
Primary outcome
Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE)
Time frame: 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
Time frame: 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.
6 secondary outcomes
Mean Change From Baseline in the Diabetic Ulcer Severity Score (DUSS)
Time frame: Baseline and Day 15 (Visit 5)
Mean Change From Baseline in the Diabetic Foot Ulcer Wound Infection Score
Time frame: Baseline; Day 15 (Visit 5)
Mean Change From Baseline in Ulcer Area in the ITT Population
Time frame: Baseline; Day 15 (Visit 5)
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the ITT Population
Time frame: Baseline; Day 15 (Visit 5)
Mean Change From Baseline in Ulcer Area in the Per-Protocol Population
Time frame: Baseline; Day 15 (Visit 5)
Mean Change From Baseline in the Percentage of Area Reduction for Ulcers in the Per-Protocol Population
Time frame: Baseline; Day 15 (Visit 5)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve Kates, PhD study director
Lakewood-Amedex Inc
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bisphosphocin Nu-3 in people with Diabetic Foot Infections, run by Lakewood-Amedex Inc at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Treatment-emergent Adverse Events as Graded According to the Common Terminology Criteria for Adverse Events v4.02 (CTCAE) (time frame: up to Day 15 (Visit 5)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2019.