A Study to Evaluate the Safety, Tolerability and Amount of Drug Levels in Blood of EI1071 in Healthy Volunteers
Study Details
Study Description
Brief Summary
This is a first-in-human study to determine the safety, tolerability, and pharmacokinetics of EI1071 after single and multiple doses in healthy volunteers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This phase 1 first-in-human study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of EI1071 when administered to healthy adult volunteers. This is a randomized, double-blind, placebo-controlled, ascending dose, multi-cohort trial. Approximately 50 healthy volunteers will be enrolled in up to 7 cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 5 will receive one dose of EI1071 or placebo. In MAD, participants in Cohorts 1 and 2 will receive multiple doses of EI1071 or placebo for 14 consecutive days. In both phases, sequential cohorts will be exposed to increasing doses of EI1071.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EI1071 Tablets EI1071 tablet(s) administered orally as single ascending dose, multiple ascending daily doses |
Drug: EI1071
EI1071 Tablet(s)
|
| Placebo Comparator: Placebo Matching placebo tablet(s) administered orally |
Drug: Matching Placebo
Matching Placebo Tablet(s)
|
Outcome Measures
Primary Outcome Measures
- After single ascending doses, number of subjects with treatment-emergent adverse events (TEAEs) in the EI1071 dose-level cohorts. [Up to 7 days]
Experience at least 1 treatment-emergent adverse event
- After multiple ascending doses, number of subjects with TEAEs in the EI1071 dose-level cohorts. [Up to 21 days]
Experience at least 1 treatment-emergent adverse event
- After multiple ascending doses, number of subjects with adverse events (AEs) leading to discontinuation in the EI1071 dose-level cohorts. [Up to 14 days]
Discontinue due to adverse event
Secondary Outcome Measures
- Cmax [Single dose: up to 48 hours; Multiple dose: up to 16 days]
Maximum observed serum concentration
- Tmax [Single dose: up to 48 hours; Multiple dose: up to 16 days]
Time to reach Cmax
- t1/2 [Single dose: up to 48 hours; Multiple dose: up to 16 days]
Terminal half-life
- AUClast [Single dose: up to 48 hours; Multiple dose: up to 16 days]
Area under the curve from the time of dosing to the time of the last measurable concentration
- AUCinf [Single dose: up to 48 hours; Multiple dose: up to 16 days]
Area under the curve from the time of dosing extrapolated to infinity
- Colony Stimulating Factor 1 (CSF1) concentration in blood after multiple-dose administration [Up to 15 days]
Amount of Colony Stimulating Factor 1
- Monocyte count in blood after multiple-dose administration [Up to 15 days]
Count of monocyte subsets
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria:
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Healthy male and female subjects, 18 to 45 years of age, inclusive.
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The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, and weighs at least 50 kg.
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The subject is in good health and has no medical condition of clinical significance or that may impact the outcome of the study, as determined by the investigator (as determined by medical history, physical examination, 12-lead electrocardiogram [ECG], vital signs, and clinical laboratory results at screening).
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The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
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The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
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The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided, and has had the opportunity to discuss the study with the investigator or designee.
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Negative pregnancy test for female subjects. Women of child bearing potential and Women not of child bearing potential are eligible to participate. Both women of child bearing potential and women of no child bearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 90 days after taking the last dose of EI1071). Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method, female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or 2 years post-menopausal. All male subjects/partners must agree to consistently and correctly use a condom. In addition, subjects may not donate sperm for the duration of the study and for 90 days after taking study drug.
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Subject is currently not using strong inhibitors or inducers of CYP3A4 and is not anticipated to use these for the duration of the study.
Exclusion Criteria:
Subjects will be eligible for enrollment in the study only if they meet NONE of the following criteria:
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The subject has a history of severe allergic or anaphylactic reactions.
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The subject has a known allergy or hypersensitivity to any component of the formulation.
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The subject has a medical history or current evidence of any clinically significant (as determined by the investigator) cardiac, endocrine (including diabetes), hematologic, hepatobiliary (abnormal alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transpeptidase [GGT], or total bilirubin), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal condition, or other major disease.
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The subject has a history of any malignant disease.
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The subject has a history of more than one herpes zoster episode or multimetameric herpes zoster.
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The subject has a history of an opportunistic infection (e.g. cytomegalovirus, pneumocystis carinii, aspergillosis, clostridium difficile).
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The subject has a history of or ongoing chronic or recurrent infectious disease (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis).
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The subject has had major trauma or surgery in the 2 months before screening or at any time between screening and check-in.
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The subject has had an acute infection within 2 weeks before screening or at any time between screening and check-in including, but not limited to, history, signs, or symptoms of a common cold (eg, mild rhinorrhea), untreated oral/dental abnormalities (e.g. untreated dental caries as determined by examination of the mouth), or untreated disruption of the skin.
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The subject has clinically significant abnormal ECG findings at screening, check-in visits, or predose, as determined by the Investigator.
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The subject has a supine blood pressure measurement outside the ranges of 90 to 140 mm Hg systolic or 45 to 90 mm Hg diastolic (measured after a rest of at least 5 minutes) at screening, check-in, or predose. Note: If either value is out of the range, blood pressure measurements may be repeated in the supine position at intervals of 5 to 10 minutes up to 3 times. If the mean systolic or diastolic measurement continues to exceed the stated limits, the subject will be excluded.
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The subject has a pulse of fewer than 45 beats per minute (bpm) or greater than 100 bpm (measured after a rest of at least 5 minutes) at screening, check-in, or predose.
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The subject tests positive for tuberculosis (TB) at screening by the QuantiFERON-TB Gold Test, or has a history of latent, inadequately treated, or active TB.
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The subject has a known history of, or a positive test result for, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) types 1 or 2 at screening.
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The subject has used prescription or over-the-counter (OTC) medication (other than ≤2 g/day paracetamol [acetaminophen] or ≤800 mg/day ibuprofen), vitamins, or herbal remedies, within 2 weeks or 5 half-lives before study drug administration, whichever is longer.
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The subject has participated in another clinical study of a new investigational drug or has received an investigational drug within the 3 months or 5 half-lives (if available) before study drug administration, whichever is longer.
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The subject has had a loss of more than 400 mL of blood (e.g. a blood donation) within 2 months before study drug administration, or has received any blood, plasma, or platelet transfusions within 3 months before check-in, or plans to donate blood during the study or within 3 months after the study.
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The subject has a history of alcohol abuse (defined as an alcohol intake more than 21 units per week) or a history of drug abuse within the 6 months before study drug administration, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 240 mL of beer, 120 mL of wine, or 1 single shot of spirits. The subject will be required to abstain from alcohol consumption 48 hours prior to screening or check-in.
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The subject is a current smoker or has a history of smoking.
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The subject has a positive test for alcohol or drugs of abuse (barbiturates, methamphetamine, benzodiazepines, morphine/opiates, phencyclidine (PCP), amphetamines, tetrahydrocannabinol (THC), methylenedioxymethamphetamine (MDMA), cocaine, methadone, and cotinine) at screening or check-in.
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The subject is unable to participate in, or successfully complete, the study, in the opinion of their general practitioner or the investigator, because the subject is any of the following:
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mentally or legally incapacitated, or unable to give consent for any reason
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in custody due to an administrative or a legal decision, or under tutelage, or being admitted to a sanitarium or social institution
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unable to be contacted in case of emergency
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unlikely to cooperate or comply with the clinical study protocol or is unsuitable for any other reason
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Parexel Early Phase Clinical Unit | Baltimore | Maryland | United States | 21225 |
Sponsors and Collaborators
- Elixiron Immunotherapeutics Inc.
- Parexel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EI1071-001