MalariaEarly Phase 1NCT03436160
Study Assessing Pharmacokinetics and Bioavailability of Three Novel Triazine Compounds
A Early Phase 1 study testing WR826647, WR909388 and WR909390 in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial summary
Open-label, randomized, microdose study Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- WR826647, WR909388 and WR909390
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2018to 3 Nov 2018
- Phase
- Early 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 19 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or non-breastfeeding female of non-childbearing potential (defined as either surgically sterilized by bilateral tubal ligation or hysterectomy with bilateral ophorectomy at least 6 months before dosing, or is one year post-menopausal, confirmed by screening follicle-stimulating hormone [FSH] serum levels consistent with postmenopausal status >30mIU/mL)
- Between the ages of 19 and 50, inclusive, at the time of screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or EKGs, as deemed by the PI or designee.
- Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
- Continuous non smoker who has not used nicotine containing products for at least 90 days prior to the first dose and throughout the study.
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dose/dosing of study drug. A male who has been vasectomized less than 4 months prior to study first dose/dosing must follow the same restrictions as a non vasectomized male).
Show all 9Show fewer
- Male volunteers must agree not to donate sperm from the first dose until 90 days after last dose.
- Ability to comprehend and willingness to sign informed consent, which includes the Authorization for the Release of Health Information document
- Willingness to comply with all study procedures including two 24-hour inpatient stays at the study clinic and returning to the clinic for scheduled follow-up visits
Who cannot join
- History of any medical or psychiatric illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
- History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds (i.e., compound in the same family).
- Positive urine drug results for alcohol, amphetamines, methamphetamines, cocaine, or opioids at screening or first check in.
- Positive results at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- Received any other investigational drug within 30 days prior to study entry. The 30 day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
Show all 16Show fewer
- An employee of the study site involved with the study
- Inability to comply with the study procedures
- Unable to refrain from or anticipate the use of any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dose and throughout the study. Acetaminophen (up to 2 g per 24 hour period may be permitted during the study but only for dosing as needed to treat adverse events (AEs).
- Unable to refrain from or anticipate the use of any drugs known to be significant inducers of cytochrome P450 (CYP) enzymes and/or permeability glycoprotein (P gp), including St. John's Wort, for 30 days prior to the first dose/dosing and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/pharmacodynamics interaction with study drug.
- Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dose and throughout the study.
- Donation of blood or significant blood loss within 56 days prior to the first dose.
- Plasma donation within 7 days prior to the first dose.
- Subjects with tattoo(s) or scarring at or near the site of IV infusion or any other condition which may interfere with infusion site examination(s), in the opinion of the Investigator or designee.
- Participation in another clinical trial in which a 14C-labeled drug was administered within 1 year prior to Day 1.
- Any other significant finding that in the opinion of the clinical investigators would make the subject's participation in the study unsafe.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploratory Microdose Study Assessing Pharmacokinetics and Bioavailability of Three Novel Triazine Compounds
Open-label, randomized, microdose study
Read the detailed description
This is an open-label, randomized, fixed-sequence, microdose study of three Carbon-14 radio labeled (14C) triazine compounds WR826647, WR909388, WR909390 designed in accordance with ICH Guidance for Industry M3(R2) (ICH 2009). Subjects will be randomized to one of three groups to receive 100 mcg WR826647, WR909388, or WR909390 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data using Phoenix WinNonlin version 6.3 or higher, and descriptive statistics assessed using SAS version 9.3 or higher. No statistical significance inferences will be made. An analysis of variance (ANOVA) will be performed on the natural logarithm (ln) transformed dose-adjusted AUCinf to estimate the bioavailability. The sample size of 6 subjects per group is considered adequate to obtain useful data to compute descriptive statistics. Interim analyses will be done after the IV dosing groups in order to assess half-lives of the 3 compounds to ensure the wash-out period between IV bolus and oral dosing is at least 6 half-lives long.
- Conditions
- Malaria
- Being tested
- WR826647, WR909388, WR909390
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WR826647Drug
Also called Triazine WR826647
100 mcg Carbon-14 radio labeled WR826647 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
WR909388Drug
Also called Triazine WR909388
100 mcg Carbon-14 radio labeled WR909388 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
WR909390Drug
Also called Triazine WR909390
100 mcg Carbon-14 radio labeled WR909309 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
| Study group | Role | What they receive |
|---|---|---|
| WR826647 | Experimental | 100 mcg Carbon-14 radio labeled WR826647 administered via IV Receives: Drug: WR826647 |
| WR909388 | Experimental | 100 mcg Carbon-14 radio labeled WR909388 administered via IV Receives: Drug: WR909388 |
| WR909390 | Experimental | 100 mcg Carbon-14 radio labeled WR909390 administered via IV Receives: Drug: WR909390 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacodynamic parameters of Carbon-14 radio labeled (14C) WR826647, WR909388, and WR909390
Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data and descriptive statistics assessed . No statistical significance inferences will be made.
Measured: 0, 5, 15 min, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours, and then daily for 1 week, and weekly until 3 weeks following dosing
Secondary outcomes (1)
Bioavailability of Carbon-14 radio labeled (14C) WR826647, WR909388, and WR909390
An analysis of variance (ANOVA) will be performed on the natural logarithm (ln) transformed dose-adjusted AUCinf to estimate the bioavailability.
Measured: 0, 5 , 15 min, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours, and then daily for 1 week, and weekly until 3 weeks following dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start10 Aug 2018
- Primary completion3 Nov 2018
- Study completion3 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to one of three groups to receive 100 mcg Carbon-14 radio labeled WR826647, WR909388, or WR909390
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- Allen Hunt, MD, Principal investigator, Celerion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436160
- Sponsor's protocol ID
- S-15-45
- Status last verified
- Mar 2019
- First submitted
- 6 Feb 2018
- Last updated
- 5 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Microdose Study Assessing Pharmacokinetics and Bioavailability of Three Novel Triazine Compounds
- ClinicalTrials.gov ID
- NCT03436160
- Acronym / sponsor ID
- S-15-45
- Conditions
- Malaria
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Study start
- 10 Aug 2018 (actual)
- Primary completion
- 3 Nov 2018 (actual)
- Study completion
- 3 Nov 2018 (actual)
- First posted
- 19 Feb 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.
Open-label, randomized, microdose study
Detailed description
This is an open-label, randomized, fixed-sequence, microdose study of three Carbon-14 radio labeled (14C) triazine compounds WR826647, WR909388, WR909390 designed in accordance with ICH Guidance for Industry M3(R2) (ICH 2009). Subjects will be randomized to one of three groups to receive 100 mcg WR826647, WR909388, or WR909390 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data using Phoenix WinNonlin version 6.3 or higher, and descriptive statistics assessed using SAS version 9.3 or higher. No statistical significance inferences will be made. An analysis of variance (ANOVA) will be performed on the natural logarithm (ln) transformed dose-adjusted AUCinf to estimate the bioavailability. The sample size of 6 subjects per group is considered adequate to obtain useful data to compute descriptive statistics. Interim analyses will be done after the IV dosing groups in order to assess half-lives of the 3 compounds to ensure the wash-out period between IV bolus and oral dosing is at least 6 half-lives long.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Subjects will be randomized to one of three groups to receive 100 mcg Carbon-14 radio labeled WR826647, WR909388, or WR909390
| Arm | Type | Receives |
|---|---|---|
| WR826647 | Experimental | Drug: WR826647100 mcg Carbon-14 radio labeled WR826647 administered via IV |
| WR909388 | Experimental | Drug: WR909388100 mcg Carbon-14 radio labeled WR909388 administered via IV |
| WR909390 | Experimental | Drug: WR909390100 mcg Carbon-14 radio labeled WR909390 administered via IV |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or non-breastfeeding female of non-childbearing potential (defined as either surgically sterilized by bilateral tubal ligation or hysterectomy with bilateral ophorectomy at least 6 months before dosing, or is one year post-menopausal, confirmed by screening follicle-stimulating hormone [FSH] serum levels consistent with postmenopausal status >30mIU/mL)
- Between the ages of 19 and 50, inclusive, at the time of screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or EKGs, as deemed by the PI or designee.
- Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
- Continuous non smoker who has not used nicotine containing products for at least 90 days prior to the first dose and throughout the study.
Key exclusion criteria (16 listed)
- History of any medical or psychiatric illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
- History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds (i.e., compound in the same family).
- Positive urine drug results for alcohol, amphetamines, methamphetamines, cocaine, or opioids at screening or first check in.
- Positive results at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
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 |
|---|---|---|
| WR826647Also: Triazine WR826647100 mcg Carbon-14 radio labeled WR826647 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long. | Drug | WR826647 |
| WR909388Also: Triazine WR909388100 mcg Carbon-14 radio labeled WR909388 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long. | Drug | WR909388 |
| WR909390Also: Triazine WR909390100 mcg Carbon-14 radio labeled WR909309 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long. | Drug | WR909390 |
Primary outcome
Pharmacodynamic parameters of Carbon-14 radio labeled (14C) WR826647, WR909388, and WR909390
Time frame: 0, 5, 15 min, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours, and then daily for 1 week, and weekly until 3 weeks following dosing
Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data and descriptive statistics assessed . No statistical significance inferences will be made.
1 secondary outcome
Bioavailability of Carbon-14 radio labeled (14C) WR826647, WR909388, and WR909390
Time frame: 0, 5 , 15 min, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours, and then daily for 1 week, and weekly until 3 weeks following dosing.
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 5 Mar 2019.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Allen Hunt, MD principal investigator
Celerion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing WR826647, WR909388 and WR909390 in people with Malaria, run by U.S. Army Medical Research and Development Command 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 16 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 5 Mar 2019. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Pharmacodynamic parameters of Carbon-14 radio labeled (14C) WR826647, WR909388, and WR909390 (time frame: 0, 5, 15 min, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours, and then daily for 1 week, and weekly until 3 weeks following dosing). 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 5 Mar 2019.