Single Oral Dose Escalation Study of DNDI-0690 in Healthy Subjects

NCT03929016 | Completed Phase 1

• 3 other identifiers: DNDi-0690-012018-002021-35QSC200932
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Visceral Leishmaniasis; Cutaneous Leishmaniases

Keywords

First-in-human; single ascending dose; healthy volunteer

Outcome Measures

Primary Outcomes (7)

• 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

  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)

  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)

  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)

  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)

  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)

  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

  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)

  pre-dose up to 72 hours post-dose

• Observed Maximum Concentration (Cmax)

  pre-dose up to 72 hours post-dose

• Time to Maximum Observed Plasma Concentration (Tmax)

  pre-dose up to 72 hours post-dose

• Apparent elimination half-life (T1/2)

  pre-dose up to 72 hours post-dose

Study Arms (11)

Active DNDI-0690 male 10mg fasting

EXPERIMENTAL

Single dose 10mg male fasting

Drug: DNDI-0690

Placebo male fasting

PLACEBO COMPARATOR

Single dose placebo male fasting

Drug: Placebo of DNDI-0690

Active DNDI-0690 male 30mg fasting

EXPERIMENTAL

Single dose 30mg male fasting

Drug: DNDI-0690

Active DNDI-0690 male 150mg fasting

EXPERIMENTAL

Single dose 150mg male fasting

Drug: DNDI-0690

Active DNDI-0690 male 400mg fasting

EXPERIMENTAL

Single dose 400mg male fasting

Drug: DNDI-0690

Active DNDI-0690 male 1200mg fasting

EXPERIMENTAL

Single dose 1200mg male fasting

Drug: DNDI-0690

Active DNDI-0690 male 3600mg fasting

EXPERIMENTAL

Single dose 3600mg male fasting

Drug: DNDI-0690

Placebo male fed

PLACEBO COMPARATOR

Placebo male fed

Drug: Placebo of DNDI-0690

Active DNDI-0690 400mg male fed

EXPERIMENTAL

Single dose 400mg male fed

Drug: DNDI-0690

Placebo female fasting

PLACEBO COMPARATOR

Placebo female fasting

Drug: Placebo of DNDI-0690

Active DNDI-0690 1200mg female fasting

EXPERIMENTAL

Single dose 1200mg female fasting

Drug: DNDI-0690

Interventions

DNDI-0690 DRUG

capsules of 10, 100 and 200 mg

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-0690 DRUG

capsules of matching placebo

Placebo female fasting; Placebo male fasting; Placebo male fed

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males (Cohorts 1 to 7) or healthy WONCBP (Cohort 8)
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Wellcome Trust: collaborator

Study Sites (1)

Quotient Sciences

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Leishmaniasis, Visceral; Leishmaniasis, Cutaneous

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sharan Sidhu, MD

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Ascending Dose

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 26, 2019
• Study Start: April 4, 2019
• Primary Completion: December 6, 2019
• Study Completion: July 2, 2020
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: at the time of publication of study results.
• Access Criteria: not yet defined

Locations

GB (1)