MalariaPhase 1NCT03490162
Safety and Pharmacokinetics Study of DM1157 to Treat Malaria
A Phase 1 study testing DM1157 in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- DM1157
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2018to 6 Sep 2019
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- History of severe drug hypersensitivity, including a severe allergic reaction, anaphylaxis, or convulsions following any medication, vaccination, or infusion.
- History of malignancy except low-grade skin cancer (ex. basal cell carcinoma thought to be cured).
- Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
- History of drug or alcohol abuse within 12 months before Screening.
- History of renal disease.
- Excessive consumption of beverages containing xanthine bases, including Red Bull, chocolate, etc., or more than 400 mg of caffeine per day (more than 4 cups of coffee per day).
- Consumption of citrus fruits or juices (ex. pomegranate, orange, lime, grapefruit) within 7 days before first study drug administration.
- Use of nicotine-containing products within 30 days before Screening and until completion of study.
- Consumption of alcohol within 24 hours of first study drug administration.
- Has any condition or disease that might affect drug absorption, distribution, or excretion (ex. gastrectomy, diarrhea).
- Positive serology results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
- Positive drug screen (cannabinoids, amphetamines, barbiturates, cocaine, opiates, benzodiazepines, phencyclidine) or positive breathalyzer test for alcohol.
- Subjects should be notified by phone not to consume any poppy seeds within 24 hours before the Screening blood test to avoid false a positive opioid test result.
- History of allergic reaction or intolerance to CQ.
- Males with a QTcF greater than 450 ms or females with a QTcF greater than 460 ms (Fridericia's correction) at Screening.
- Positive pregnancy test within 24 hours before study drug administration; pregnant or nursing.
- Screening lab tests, specifically total WBC, platelet count, hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine, which meet Grade 1 or higher toxicity. Safety laboratory tests drawn on Day -1 will serve as baseline. Day -1 safety laboratory tests with a Grade 1 severity will not exclude a subject from participation if assessed as not clinically significant by the PI or designee.
- Any specific condition that, in the judgment of the site PI, precludes participation because it could affect subject safety.
- Received an experimental agent within 30 days or 5 half-lives (whichever is longer) before study drug administration.
- Vaccine, drug, biologic, device, blood product, or medication
- Is participating or plans to participate in another clinical study with an interventional agent that will be received during participation in this study.
- Has donated more than 500 mL of blood within the last month before Screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
Durham, North Carolina, 27710
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses and Effect of Food on the Pharmacokinetics of DM1157 in Healthy Adults
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.
Read the detailed description
This is a first-in-humans, phase 1, randomized, double-blind, single-site, placebo-controlled study in 104 healthy volunteers, males and females, aged 18 to 45 years inclusive. The study will consists of 3 parts: Part 1, Single Ascending Dose (SAD) - participants will be administered a single dose (ranges from 9 mg to 900 mg) of DM1157 orally after fasting or a matching placebo; Part 2, Multiple Ascending Dose (MAD) - participants will be administered three doses (ranges from 150 mg to 900 mg) of DM1157 orally once daily for three days after fasting or a matching placebo; and Part 3, Food Effect - participants will be administered 300 mg of DM1157 orally with high fat meal or a matching placebo. 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. The secondary objectives are to: 1) assess the PK of single doses of DM1157 at levels ranging from 9 mg to 900 mg, including dose proportionality; 2) assess the PK of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the PK of 300 mg DM1157 administered with or without food, including determination of the presence or absence of a food effect on exposure.
- Conditions
- Malaria
- Being tested
- DM1157, Placebo
- Keywords
- Anti-Malarial, DM1157, Pharmacokinetics, Safety
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DM1157Drug
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.
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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) Receives: Drug: DM1157; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Count of participants who discontinued single ascending dose (SAD) for safety reasons
Measured: 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
Measured: Day 1 through Day 14
Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)
Measured: Day 1 through Day 18
Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)
Measured: 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
Measured: Day 1 through Day 14
Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)
Measured: Day 1 through Day 18
Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)
Measured: Day 1 through Day 14
Occurrence of Adverse Events (AE) for a single dose taken after food ingestion
Measured: Day 1 through Day 14
Occurrence of Adverse Events (AE) for multiple ascending dose (MAD)
Measured: Day 1 through Day 18
Occurrence of Adverse Events (AE) for single ascending dose (SAD)
Measured: Day 1 through Day 14
Occurrence of laboratory Adverse Events (AE) for a single dose taken after food ingestion
Measured: Day 1 through Day 14
Occurrence of laboratory Adverse Events (AE) for multiple ascending dose (MAD)
Measured: Day 1 through Day 18
Occurrence of laboratory Adverse Events (AE) for single ascending dose (SAD)
Measured: Day 1 through Day 14
Secondary outcomes (3)
Plasma levels of a single dose of DM1157 taken after food ingestion
Measured: Day 1 through Day 14
Plasma levels of multiple ascending dose (MAD) of DM1157
Measured: Day 1 through Day 18
Plasma levels of single ascending dose (SAD) of DM1157
Measured: Day 1 through Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2018
- Study start31 Jul 2018
- Primary completion6 Sep 2019
- Study completion6 Sep 2019
Why it stopped: There was toxicity in higher dose groups and a therapeutic dose level was not found in lower dose groups.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03490162
- Sponsor's protocol ID
- 16-0088
- Other IDs
- HHSN272201500006I
- Status last verified
- 30 Apr 2019
- First submitted
- 29 Mar 2018
- Last updated
- 23 Jul 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 35184256
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses and Effect of Food on the Pharmacokinetics of DM1157 in Healthy Adults
- ClinicalTrials.gov ID
- NCT03490162
- Acronym / sponsor ID
- 16-0088
- Conditions
- Malaria
- Keywords
- Anti-Malarial, DM1157, Pharmacokinetics, Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: There was toxicity in higher dose groups and a therapeutic dose level was not found in lower dose groups.
- Enrolment
- 50 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 31 Jul 2018 (actual)
- Primary completion
- 6 Sep 2019 (actual)
- Study completion
- 6 Sep 2019 (actual)
- First posted
- 6 Apr 2018 (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 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.
Detailed description
This is a first-in-humans, phase 1, randomized, double-blind, single-site, placebo-controlled study in 104 healthy volunteers, males and females, aged 18 to 45 years inclusive. The study will consists of 3 parts: Part 1, Single Ascending Dose (SAD) - participants will be administered a single dose (ranges from 9 mg to 900 mg) of DM1157 orally after fasting or a matching placebo; Part 2, Multiple Ascending Dose (MAD) - participants will be administered three doses (ranges from 150 mg to 900 mg) of DM1157 orally once daily for three days after fasting or a matching placebo; and Part 3, Food Effect - participants will be administered 300 mg of DM1157 orally with high fat meal or a matching placebo. 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. The secondary objectives are to: 1) assess the PK of single doses of DM1157 at levels ranging from 9 mg to 900 mg, including dose proportionality; 2) assess the PK of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the PK of 300 mg DM1157 administered with or without food, including determination of the presence or absence of a food effect on exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Food Effect | Experimental | Drug: DM1157, Other: Placebo300 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 |
| MAD 1 | Experimental | Drug: DM1157, Other: Placebo150 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 |
| MAD 2 | Experimental | Drug: DM1157, Other: Placebo300 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 |
| MAD 3 | Experimental | Drug: DM1157, Other: Placebo600 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 |
| MAD 4 | Experimental | Drug: DM1157, Other: Placebo900 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 |
| SAD 1 | Experimental | Drug: DM1157, Other: Placebo9 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 |
| SAD 2 | Experimental | Drug: DM1157, Other: Placebo27 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 |
| SAD 3 | Experimental | Drug: DM1157, Other: Placebo81 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 |
| SAD 4 | Experimental | Drug: DM1157, Other: Placebo150 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 |
| SAD 5 | Experimental | Drug: DM1157, Other: Placebo300 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 |
| SAD 6 | Experimental | Drug: DM1157, Other: Placebo600 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 |
| SAD 7 | Experimental | Drug: DM1157, Other: Placebo900 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) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (37 listed)
- 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.
- 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.
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 |
|---|---|---|
| DM1157DM1157 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. | Drug | Food Effect, MAD 1, MAD 2, MAD 3, MAD 4, SAD 1, SAD 2, SAD 3, SAD 4, SAD 5, SAD 6, SAD 7 |
| PlaceboPlacebo | Other | Food Effect, MAD 1, MAD 2, MAD 3, MAD 4, SAD 1, SAD 2, SAD 3, SAD 4, SAD 5, SAD 6, SAD 7 |
Primary outcome
Count of participants who discontinued single ascending dose (SAD) for safety reasons
Time frame: 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
Time frame: Day 1 through Day 14
Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)
Time frame: Day 1 through Day 18
Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)
Time frame: 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
Time frame: Day 1 through Day 14
Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD)
Time frame: Day 1 through Day 18
Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD)
Time frame: Day 1 through Day 14
Occurrence of Adverse Events (AE) for a single dose taken after food ingestion
Time frame: Day 1 through Day 14
Occurrence of Adverse Events (AE) for multiple ascending dose (MAD)
Time frame: Day 1 through Day 18
Occurrence of Adverse Events (AE) for single ascending dose (SAD)
Time frame: Day 1 through Day 14
Occurrence of laboratory Adverse Events (AE) for a single dose taken after food ingestion
Time frame: Day 1 through Day 14
Occurrence of laboratory Adverse Events (AE) for multiple ascending dose (MAD)
Time frame: Day 1 through Day 18
Occurrence of laboratory Adverse Events (AE) for single ascending dose (SAD)
Time frame: Day 1 through Day 14
3 secondary outcomes
Plasma levels of a single dose of DM1157 taken after food ingestion
Time frame: Day 1 through Day 14
Plasma levels of multiple ascending dose (MAD) of DM1157
Time frame: Day 1 through Day 18
Plasma levels of single ascending dose (SAD) of DM1157
Time frame: Day 1 through Day 14
Results and safety
The study was stopped early (reason given: There was toxicity in higher dose groups and a therapeutic dose level was not found in lower dose groups.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
- Derived from this study: PubMed 35184256Balevic 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 DM1157 in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 9 inclusion and 37 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: stopped early, as of the sponsor's last update on 23 Jul 2021. 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 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. 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 was stopped early (reason given: There was toxicity in higher dose groups and a therapeutic dose level was not found in lower dose groups.). Results are not available in the source record.
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?
Count of participants who discontinued single ascending dose (SAD) for safety reasons (time frame: Day 1 through Day 14). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03490162, which also lists 1 linked publication.
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 23 Jul 2021.