Clinical Trial Results:
A phase 2, randomized, double blind, vehicle controlled, parallel group study to explore the efficacy, pharmacodynamics and safety of topical ionic contra-viral therapy (ICVT), comprised of digoxin and furosemide in healthy volunteers with actinic keratosis
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Summary
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EudraCT number |
2018-000034-36 |
Trial protocol |
NL |
Global end of trial date |
31 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Sep 2022
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First version publication date |
20 Sep 2022
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Other versions |
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Summary report(s) |
M3. CHDR1734_CSR_Summary_15Jun2020 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CHDR1734_CLS003-CO-PR-004
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
ToetsingOnline: NL6461 3.056.18 | ||
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Sponsors
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Sponsor organisation name |
Maruho Co., Ltd
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Sponsor organisation address |
93 Chudoji Awatacho , Kyoto, Japan, 600-8815
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Public contact |
Principal Investigator, Centre for Human Drug Research, +31 715246400, clintrials@chdr.nl
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Scientific contact |
Principal Investigator, Centre for Human Drug Research, +31 715246400, clintrials@chdr.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary Objective
- To explore the pharmacodynamics of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent) in patients with AK.
- To evaluate clinical efficacy of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent), and vehicle gel.
Secondary Objectives
- To evaluate the safety and tolerability of ICVT comprised of digoxin and furosemide (dualagent), digoxin (single agent), furosemide (single agent).
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Protection of trial subjects |
CLS003 consists of a combination of the active substances digoxin and furosemide. The cardiac glycoside digoxin and the loop diuretic furosemide are currently market registered drugs for various indications e.g. heart failure / atrium fibrillation and hypertension, respectively. The formulations on the market comprise oral and parenteral route of administration leading to high systemic exposure to both drugs. Consequently, there is a vast amount of pre-clinical and clinical experience with these mechanisms of action. Therefore, drugs of this class can be administered safely to healthy volunteers and patients in a topical formulation.
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Background therapy |
We hypothesized that topical ionic contra-viral therapy, comprised of digoxin (0.125%) and furosemide (0.125%), could serve as a potential treatment for HPV-mediated and associated diseases. The ionic properties of digoxin and furosemide interact with the cell membrane ion cotransporters Na+/K+-ATPase and Na+-K+-2Cl- co-transporter-1 and thereby inhibit the K+ influx on which DNA viruses rely for replication. | ||
Evidence for comparator |
Vehicle gel with identical appearance will serve as placebo. | ||
Actual start date of recruitment |
22 Oct 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 32
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
25
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85 years and over |
0
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Recruitment
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Recruitment details |
Screenings started at 22-OCT-2018 and the last screening was at 18-JUN-2019 CHDR, Leiden, the Netherlands. | |||||||||
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Pre-assignment
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Screening details |
Male and female subjects ≥ 18 years with a condition of general good health (with the exception of AK). The health status was verified by absence of evidence of any clinically significant active or uncontrolled chronic disease other than AK. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active drugs | |||||||||
Arm description |
The patients were randomized 1:1:1:1 for the four treatment arms in blocks of 4. Per patient two AK fields were selected; one AK field was treated with the topical formulation and the other AK field was used as untreated comparator. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Digoxin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
Subject received tubes of 5g. Once daily for 42 consecutive days, a drop in the form a small pea was applied on the treatment field of 25-35 cm2.
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Investigational medicinal product name |
Furosemide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
Subject received tubes of 5g. Once daily for 42 consecutive days, a drop in the form a small pea was applied on the treatment field of 25-35 cm2.
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Investigational medicinal product name |
ICVT
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
Subject received tubes of 5g. Once daily for 42 consecutive days, a drop in the form a small pea was applied on the treatment field of 25-35 cm2.
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Arm title
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Placebo | |||||||||
Arm description |
The patients were randomized 1:1:1:1 for the four treatment arms in blocks of 4. Per patient two AK fields were selected; one AK field was treated with the topical formulation and the other AK field was used as untreated comparator. less | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
Subject received tubes of 5g. Once daily for 42 consecutive days, a drop in the form a small pea was applied on the treatment field of 25-35 cm2.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial (overall period)
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Reporting group description |
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End points reporting groups
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Reporting group title |
Active drugs
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Reporting group description |
The patients were randomized 1:1:1:1 for the four treatment arms in blocks of 4. Per patient two AK fields were selected; one AK field was treated with the topical formulation and the other AK field was used as untreated comparator. | ||
Reporting group title |
Placebo
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Reporting group description |
The patients were randomized 1:1:1:1 for the four treatment arms in blocks of 4. Per patient two AK fields were selected; one AK field was treated with the topical formulation and the other AK field was used as untreated comparator. less | ||
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End point title |
Total clearance present/absent at EOT and/or EOS [1] | |||||||||
End point description |
No total clearance was present at the end of study for any subject.
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End point type |
Primary
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End point timeframe |
42 Days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See attachment. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Screening until end of study.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
Digoxin/Furosemide/ICVT/Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Mar 2019 |
Change made in the protocol concerning the minimal amount of Actinic Keratosis (AK) lesions required to enroll into the study. |
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09 Aug 2019 |
Change of sponsor for this study from Cutanea Life Sciences to Maruho Co., Ltd. ln June 2019, Maruho acquired Cutanea Life Sciences as a wholly-owned subsidiar yand with that took over the R&D activities of Cutanea Life Sciences, including the current study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
