Visceral LeishmaniasisPhase 1NCT03929016
Single Oral Dose Escalation Study of DNDI-0690 in Healthy Subjects
A Phase 1 study testing DNDI-0690 in people with Visceral Leishmaniasis and Cutaneous Leishmaniases, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
Trial summary
This study will evaluate how the test medicine DNDI-0690 is taken up and broken down by the body and will also look at the safety and tolerability of the test medicine after a single dose. This is the first time the test medicine DNDI-0690 will be administered to humans. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Visceral Leishmaniasis, Cutaneous Leishmaniases
- What is being tested?
- DNDI-0690
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Apr 2019to 2 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males (Cohorts 1 to 7) or healthy WONCBP (Cohort 8)
- 18 to 55 years (Cohorts 1 to 7) or 18 to 60 years (Cohort 8)of age at the time of signing informed consent
- Body mass index (BMI) of 18.0 to 30.1 kg/m2 as measured at screening
- General good physical health determined by medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory tests
- Normal blood pressure: Systolic blood pressure between ≥90 and ≤140 mmHg, Diastolic blood pressure ≤90 mmHg, measured after 10 min rest in supine position at screening, admission and pre-dose
- A resting Heart Rate (HR) between ≥40 and ≤90 bpm measured after 10 min rest in supine position at screening, admission and pre-dose
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- ECG recording without clinically significant abnormality, including QTcF measure of ≤450 msec (male) or ≤470 msec (female) at screening, admission and pre-dose
- Having had no febrile seizures or infectious illness for at least 7 days prior to administration of the Investigational Medicinal Product (IMP)
- Must be willing and able to communicate and participate in the whole study
- Must provide written informed consent
- Must agree to adhere to the contraception requirements and life-style restrictions defined in the protocol
Who cannot join
- Subjects who have received any IMP in a clinical research study within the 3 months or 90 days prior to Day 1
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- Subjects who have previously been enrolled in this study and/or have received DNDI-0690 previously
- History of any drug or alcohol abuse in the past 2 years
- Demonstrating excess in caffeine/xanthine consumption (more than 6 cups of coffee or equivalent a day)
- Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type). As confirmed by a positive alcohol breath test at screening or admission
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- Current smokers and those who have smoked within the last 12 months. As confirmed by a breath carbon monoxide reading of greater than 10 ppm at screening or admission
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation, bilateral tubal occlusion and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration ≥40 IU/L)
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
- Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis (especially aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), creatinine, and blood urea nitrogen (BUN)) as judged by the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert's syndrome are allowed
- Confirmed positive drugs of abuse test result
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- Evidence of renal impairment at screening or admission, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation
- History of clinically significant cardiovascular, renal, hepatic, neurological (especially seizures), immunological, psychiatric, myopathies, bleeding tendency, respiratory and particularly gastrointestinal (GI) disease, especially peptic ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome, as judged by the investigator
- History of additional risk factors for Torsades des Pointe (eg heart failure, hypokalaemia, family history of long QT syndrome)
- Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency
- Any relevant GI complaints within 7 days of dosing
- Subjects with a history of cholecystectomy or gall stones (Cohort 7 only)
- Serious adverse reaction or clinically relevant hypersensitivity to any drug or the formulation excipients (Hypromellose [HPMC], sodium lauryl sulphate [SLS], sucrose, croscarmellose sodium and magnesium stearate)
- Presence or history of clinically significant allergy requiring treatment (including asthma, urticaria, clinically significant allergic rash or other severe allergic diathesis), as judged by the investigator. Hay fever is allowed unless it is active
- Donation or loss of greater than 500 mL of blood within the previous 3 months or more than 100 mL within 30 days before signing Informed Consent Form (ICF) to this trial
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug (including anti-acid drugs) or vitamins/herbal remedies (eg St. John's Wort and others which are known to interfere with the Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) metabolic pathways) or HRT in the 21 days before IMP administration. Administration of up to 4 g of paracetamol per day within 7 days of IMP administration is allowed
- Surgery within 12 weeks prior to screening, with the exception of appendectomy
- Any surgery (eg gastric bypass) or medical condition that may affect absorption of orally administered drugs
- Failure to satisfy the investigator of fitness to participate for any other reason
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Double-blind, Randomised, Single Centre, Parallel Group, Single-dose, Dose-escalation, Placebo Controlled Study of the Safety, Tolerability and Pharmacokinetics of DNDI-0690 After Oral Dosing in Healthy Subjects
This study will evaluate how the test medicine DNDI-0690 is taken up and broken down by the body and will also look at the safety and tolerability of the test medicine after a single dose. This is the first time the test medicine DNDI-0690 will be administered to humans.
Read the detailed description
DNDI-0690 is intended to be used as oral treatment for Visceral Leishmaniasis with potential for the cutaneous form of the disease, Cutaneous Leishmaniasis. The present protocol describes the first-in-human (FIH) study with DNDI-0690.
- Conditions
- Visceral Leishmaniasis, Cutaneous Leishmaniases
- Being tested
- DNDI-0690, Placebo of DNDI-0690
- Keywords
- First-in-human, single ascending dose, healthy volunteer
- Medical subject headings
- Leishmaniasis, Visceral, Leishmaniasis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNDI-0690Drug
capsules of 10, 100 and 200 mg
Placebo of DNDI-0690Drug
capsules of matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Active DNDI-0690 male 10mg fasting | Experimental | Single dose 10mg male fasting Receives: Drug: DNDI-0690 |
| Placebo male fasting | Placebo comparator | Single dose placebo male fasting Receives: Drug: Placebo of DNDI-0690 |
| Active DNDI-0690 male 30mg fasting | Experimental | Single dose 30mg male fasting Receives: Drug: DNDI-0690 |
| Active DNDI-0690 male 150mg fasting | Experimental | Single dose 150mg male fasting Receives: Drug: DNDI-0690 |
| Active DNDI-0690 male 400mg fasting | Experimental | Single dose 400mg male fasting Receives: Drug: DNDI-0690 |
| Active DNDI-0690 male 1200mg fasting | Experimental | Single dose 1200mg male fasting Receives: Drug: DNDI-0690 |
| Active DNDI-0690 male 3600mg fasting | Experimental | Single dose 3600mg male fasting Receives: Drug: DNDI-0690 |
| Placebo male fed | Placebo comparator | Placebo male fed Receives: Drug: Placebo of DNDI-0690 |
| Active DNDI-0690 400mg male fed | Experimental | Single dose 400mg male fed Receives: Drug: DNDI-0690 |
| Placebo female fasting | Placebo comparator | Placebo female fasting Receives: Drug: Placebo of DNDI-0690 |
| Active DNDI-0690 1200mg female fasting | Experimental | Single dose 1200mg female fasting Receives: Drug: DNDI-0690 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of DNDI-0690 by Assessing the Occurrence of Treatment-emergent adverse events (TEAEs)
number of subjects experiencing TEAEs classified by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class and Preferred Terms
Measured: from baseline up to 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes in 12-lead electrocardiogram (ECG) parameters
corrected QT interval by Frideriecia's formula (QTcF) (msec)
Measured: from baseline up to 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function
aspartate aminotransferase (AST)
Measured: from baseline up 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function
alanine aminotransferase (ALT)
Measured: from baseline up 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function
creatinine (mg/dL)
Measured: from baseline up 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function
creatinine clearance (CLcr)
Measured: from baseline up 7-10 days post-dose
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Troponin I as a cardiac safety marker
Troponin I
Measured: 4h, 9h, 24h and 48h post-dose
Secondary outcomes (4)
Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity (AUC0-inf)
To assess plasma pharmacokinetic parameters
Measured: pre-dose up to 72 hours post-dose
Observed Maximum Concentration (Cmax)
To assess plasma pharmacokinetic parameters
Measured: pre-dose up to 72 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax)
To assess plasma pharmacokinetic parameters
Measured: pre-dose up to 72 hours post-dose
Apparent elimination half-life (T1/2)
To assess plasma pharmacokinetic parameters
Measured: pre-dose up to 72 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start4 Apr 2019
- Primary completion6 Dec 2019
- Study completion2 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Visceral LeishmaniasisStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Single Ascending Dose
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Sharan Sidhu, MD, Principal investigator, Quotient Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03929016
- Sponsor's protocol ID
- DNDi-0690-01
- Other IDs
- 2018-002021-35, QSC200932, 2018
- Status last verified
- Dec 2022
- First submitted
- 9 Apr 2019
- Last updated
- 20 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in the publication will be shared at the time of publication of study results.
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Double-blind, Randomised, Single Centre, Parallel Group, Single-dose, Dose-escalation, Placebo Controlled Study of the Safety, Tolerability and Pharmacokinetics of DNDI-0690 After Oral Dosing in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03929016
- Acronym / sponsor ID
- DNDi-0690-01
- Conditions
- Visceral Leishmaniasis, Cutaneous Leishmaniases
- Keywords
- First-in-human, single ascending dose, healthy volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 2 Jul 2020 (actual)
- First posted
- 26 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate how the test medicine DNDI-0690 is taken up and broken down by the body and will also look at the safety and tolerability of the test medicine after a single dose. This is the first time the test medicine DNDI-0690 will be administered to humans.
Detailed description
DNDI-0690 is intended to be used as oral treatment for Visceral Leishmaniasis with potential for the cutaneous form of the disease, Cutaneous Leishmaniasis. The present protocol describes the first-in-human (FIH) study with DNDI-0690.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
- Model description
- Single Ascending Dose
| Arm | Type | Receives |
|---|---|---|
| Active DNDI-0690 male 10mg fasting | Experimental | Drug: DNDI-0690Single dose 10mg male fasting |
| Placebo male fasting | Placebo comparator | Drug: Placebo of DNDI-0690Single dose placebo male fasting |
| Active DNDI-0690 male 30mg fasting | Experimental | Drug: DNDI-0690Single dose 30mg male fasting |
| Active DNDI-0690 male 150mg fasting | Experimental | Drug: DNDI-0690Single dose 150mg male fasting |
| Active DNDI-0690 male 400mg fasting | Experimental | Drug: DNDI-0690Single dose 400mg male fasting |
| Active DNDI-0690 male 1200mg fasting | Experimental | Drug: DNDI-0690Single dose 1200mg male fasting |
| Active DNDI-0690 male 3600mg fasting | Experimental | Drug: DNDI-0690Single dose 3600mg male fasting |
| Placebo male fed | Placebo comparator | Drug: Placebo of DNDI-0690Placebo male fed |
| Active DNDI-0690 400mg male fed | Experimental | Drug: DNDI-0690Single dose 400mg male fed |
| Placebo female fasting | Placebo comparator | Drug: Placebo of DNDI-0690Placebo female fasting |
| Active DNDI-0690 1200mg female fasting | Experimental | Drug: DNDI-0690Single dose 1200mg female fasting |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy males (Cohorts 1 to 7) or healthy WONCBP (Cohort 8)
- 18 to 55 years (Cohorts 1 to 7) or 18 to 60 years (Cohort 8)of age at the time of signing informed consent
- Body mass index (BMI) of 18.0 to 30.1 kg/m2 as measured at screening
- General good physical health determined by medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory tests
- Normal blood pressure: Systolic blood pressure between ≥90 and ≤140 mmHg, Diastolic blood pressure ≤90 mmHg, measured after 10 min rest in supine position at screening, admission and pre-dose
Key exclusion criteria (26 listed)
- Subjects who have received any IMP in a clinical research study within the 3 months or 90 days prior to Day 1
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- Subjects who have previously been enrolled in this study and/or have received DNDI-0690 previously
- History of any drug or alcohol abuse in the past 2 years
- Demonstrating excess in caffeine/xanthine consumption (more than 6 cups of coffee or equivalent a day)
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 |
|---|---|---|
| DNDI-0690capsules of 10, 100 and 200 mg | Drug | Active DNDI-0690 1200mg female fasting, Active DNDI-0690 400mg male fed, Active DNDI-0690 male 10mg fasting, Active DNDI-0690 male 1200mg fasting, Active DNDI-0690 male 150mg fasting, Active DNDI-0690 male 30mg fasting, Active DNDI-0690 male 3600mg fasting, Active DNDI-0690 male 400mg fasting |
| Placebo of DNDI-0690capsules of matching placebo | Drug | Placebo female fasting, Placebo male fasting, Placebo male fed |
Primary outcome
Safety and Tolerability of DNDI-0690 by Assessing the Occurrence of Treatment-emergent adverse events (TEAEs)
Time frame: from baseline up to 7-10 days post-dose
number of subjects experiencing TEAEs classified by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class and Preferred Terms
Safety and Tolerability of DNDI-0690 by Assessing the Changes in 12-lead electrocardiogram (ECG) parameters
Time frame: from baseline up to 7-10 days post-dose
corrected QT interval by Frideriecia's formula (QTcF) (msec)
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function
Time frame: from baseline up 7-10 days post-dose
aspartate aminotransferase (AST)
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function
Time frame: from baseline up 7-10 days post-dose
alanine aminotransferase (ALT)
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function
Time frame: from baseline up 7-10 days post-dose
creatinine (mg/dL)
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function
Time frame: from baseline up 7-10 days post-dose
creatinine clearance (CLcr)
Safety and Tolerability of DNDI-0690 by Assessing the Changes of Troponin I as a cardiac safety marker
Time frame: 4h, 9h, 24h and 48h post-dose
Troponin I
4 secondary outcomes
Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity (AUC0-inf)
Time frame: pre-dose up to 72 hours post-dose
Observed Maximum Concentration (Cmax)
Time frame: pre-dose up to 72 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: pre-dose up to 72 hours post-dose
Apparent elimination half-life (T1/2)
Time frame: pre-dose up to 72 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in the publication will be shared at the time of publication of study results.
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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.
Sharan Sidhu, MD principal investigator
Quotient Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DNDI-0690 in people with Visceral Leishmaniasis and Cutaneous Leishmaniases, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
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 26 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 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and Tolerability of DNDI-0690 by Assessing the Occurrence of Treatment-emergent adverse events (TEAEs) (time frame: from baseline up to 7-10 days post-dose). The study lists 7 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 20 Dec 2022.