Safety and Pharmacokinetics Study of DM1157 to Treat Malaria

NCT03490162 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 16-0088HHSN272201500006I
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 trial to evaluate the safety and pharmacokinetics of single and multiple ascending doses and effect of food on the pharmacokinetics of a novel antimalarial drug in healthy adults. The study will enroll 104 healthy volunteers, males and females, aged 18 to 45 years and will consists of 3 parts: Part 1, Single Ascending Dose (SAD); Part 2, Multiple Ascending Dose (MAD); and Part 3, Food Effect. Part 2 and Part 3 may be initiated after a Safety Monitoring Committee (SMC) review and approval of the of Part 1 safety data. Study duration will be 16 months with patient participation duration 14 days for SAD and Food Effect, and 18 days for MAD. The primary objectives of this study are to: 1) assess the safety and tolerability of single doses of DM1157 at levels ranging from 9 mg to 900 mg; 2) assess the safety and tolerability of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the safety and tolerability of DM1157 administered with or without food.

Conditions

Malaria

Keywords

Anti-Malarial; DM1157; Pharmacokinetics; Safety

Outcome Measures

Primary Outcomes (13)

• Count of participants who discontinued single ascending dose (SAD) for safety reasons

  Day 1 through Day 14

• Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for a single dose taken after food ingestion

  Day 1 through Day 14

• Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)

  Day 1 through Day 18

• Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)

  Day 1 through Day 14

• Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for a single dose taken after food ingestion

  Day 1 through Day 14

• Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)

  Day 1 through Day 18

• Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)

  Day 1 through Day 14

• Occurrence of Adverse Events (AE) for a single dose taken after food ingestion

  Day 1 through Day 14

• Occurrence of Adverse Events (AE) for multiple ascending dose (MAD)

  Day 1 through Day 18

• Occurrence of Adverse Events (AE) for single ascending dose (SAD)

  Day 1 through Day 14

• Occurrence of laboratory Adverse Events (AE) for a single dose taken after food ingestion

  Day 1 through Day 14

• Occurrence of laboratory Adverse Events (AE) for multiple ascending dose (MAD)

  Day 1 through Day 18

• Occurrence of laboratory Adverse Events (AE) for single ascending dose (SAD)

  Day 1 through Day 14

Secondary Outcomes (3)

• Plasma levels of a single dose of DM1157 taken after food ingestion

  Day 1 through Day 14

• Plasma levels of multiple ascending dose (MAD) of DM1157

  Day 1 through Day 18

• Plasma levels of single ascending dose (SAD) of DM1157

  Day 1 through Day 14

Study Arms (12)

Food Effect

EXPERIMENTAL

300 mg of DM1157 (2 capsules of 150 mg) orally with high fat diet, n=6, and matching placebo (2 capsules) orally with high fat diet, n=2

Drug: DM1157; Other: Placebo

MAD 1

EXPERIMENTAL

150 mg of DM1157 (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

MAD 2

EXPERIMENTAL

300 mg of DM1157 (2 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (2 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

MAD 3

EXPERIMENTAL

600 mg of DM1157 (4 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (4 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

MAD 4

EXPERIMENTAL

900 mg of DM1157 (6 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (6 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 1

EXPERIMENTAL

9 mg of DM1157 (1 capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 2

EXPERIMENTAL

27 mg of DM1157 (3 capsules of 9 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (3 capsules) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 3

EXPERIMENTAL

81 mg of DM1157 (9 capsules of 9 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (9 capsule) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 4

EXPERIMENTAL

150 mg of DM1157 (1capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 5

EXPERIMENTAL

300 mg of DM1157 (2 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (2 capsules) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 6

EXPERIMENTAL

600 mg of DM1157 (4 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (4 capsules) orally with 240 ml of water after an overnight fast, n=2

Drug: DM1157; Other: Placebo

SAD 7

EXPERIMENTAL

900 mg of DM1157 (6 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (6 capsules) orally with 240 ml of water after an overnight fast (n=2)

Drug: DM1157; Other: Placebo

Interventions

DM1157 DRUG

DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Food Effect; MAD 1; MAD 2; MAD 3; MAD 4; SAD 1; SAD 2; SAD 3; SAD 4; SAD 5; SAD 6; SAD 7

Placebo OTHER

Placebo

Food Effect; MAD 1; MAD 2; MAD 3; MAD 4; SAD 1; SAD 2; SAD 3; SAD 4; SAD 5; SAD 6; SAD 7

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a healthy male or nonpregnant female age 18 to 45 years, inclusive.
• Can understand the informed consent process and procedures.
• Agrees to be available for all study visits.
• If a woman of childbearing potential, agrees to use 2 acceptable contraception methods from 30 days before first study drug administration until 90 days after last study drug administration.
• Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, nonsurgical, nonhormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or less than 1 year of the last menses if menopausal.
• \-- Includes, but is not limited to, nonmale sexual relationships, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more before the subject receives the first study drug dose, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives. If sexually active, methods can include condoms, spermicidal gel, diaphragm, hormonal or nonhormonal intrauterine device, surgical sterilization, oral contraceptive pill, and depot progesterone injections.
• If male, agrees to use a barrier method of birth control from 30 days before first study drug administration until 90 days after last study drug administration.
• Has adequate venous access for blood draws.
• Body mass index (BMI) 18 to 35 kg/m\^2, inclusive.

You may not qualify if:

• Any medical disease or condition that, in the opinion of the site PI or appropriate sub investigator, is a contraindication to study participation.
• History of clinically significant ECG abnormalities or has clinically significant ECG abnormalities at Screening.
• Use of any prescription medication (excluding oral contraceptive pills in females) within 14 days before first study drug administration.
• Use of occasional nonprescription drugs (oral or topical) within 7 days before first study drug administration unless permitted by the investigator.
• \- Nonprescription drugs include vitamins, antacids, herbal or dietary supplements, and topical gels, creams, etc., that in the opinion of the site PI could interfere with the study drug.
• Hypertension with confirmed systolic blood pressure (BP) greater than 145 mm Hg or confirmed diastolic BP greater than 90 mm Hg, measured after 10 to 15 minutes of rest.
• Heart rate (HR) less than 50 bpm or greater than 100 bpm.
• Body weight less than 50 kg.
• History of a significant illness within 2 weeks before dosing (subjects can screen after illness is resolved for 2 weeks).
• History of hemolytic anemia.
• History of retinal eye disease.
• History of hearing loss.
• History of seizures.
• History of thyroid disease or currently on replacement therapy for hypothyroidism.
• History of liver disease other than Gilbert's syndrome.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Balevic SJ, Raja SM, Randell R, Deye GA, Conrad T, Nakamura A, Peyton DH, Shotwell S, Liebman K, Cohen-Wolkowiez M, Guptill JT. Adverse Reactions in a Phase 1 Trial of the Anti-Malarial DM1157: An Example of Pharmacokinetic Modeling and Simulation Guiding Clinical Trial Decisions. Infect Dis Ther. 2022 Apr;11(2):841-852. doi: 10.1007/s40121-022-00605-z. Epub 2022 Feb 20.

  PMID: 35184256 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 6, 2018
• Study Start: July 31, 2018
• Primary Completion: September 6, 2019
• Study Completion: September 6, 2019
• Last Updated: July 23, 2021

Record last verified: 2019-04-30

Locations

US (1)