- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05460065
Single and Multiple Intravenous Administrations of Estetrol (E4) in Healthy Adult Volunteers
A Double-blind, Placebo-controlled Phase I Study to Characterize the Safety, Tolerability and Pharmacokinetics (PK) of Estetrol (E4) After Single and Multiple Intravenous Administrations in Healthy Adult Volunteers
The Sponsor intends to develop an intravenous (i.v.) formulation of E4 for the treatment of neonatal hypoxic-ischemic encephalopathy (NHIE).
E4 has not been administered intravenously to humans yet.
This single-center, double-blind, placebo-controlled randomized study aims to evaluate the safety, tolerability, and PK of an i.v. E4 solution administered as single-dose or multiple dose to healthy adult volunteers.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Neuralis
- Phone Number: +3243492822
- Email: clinical.trials@mithra.com
Study Locations
-
-
-
Sofia, Bulgaria, 1612
- Recruiting
- MC Comac Medical Ltd
-
Contact:
- Dobrin Sviranov, Prof
- Phone Number: +359 885 353 009
- Email: dobrin.svinarov@comac-medical.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Premenopausal women aged 18-45 years of age who are not taking oral contraceptives or
- Men aged 18-60 years of age who are willing to use adequate contraception from screening until 4 weeks after the last dose of study treatment;
- Body mass index (BMI) >18.0 kg/m2 and <30.0 kg/m2, and body weight ≥45.0 kg;
- Continuous non-smokers who have not used tobacco or nicotine-containing products within 3 months prior to screening. Urine cotinine level at screening <200 ng/mL;
- Able and willing to abstain from tobacco, alcohol-, caffeine-, and xanthine-containing beverages or food (e.g., coffee, tea, cola, chocolate, energy drinks) from 48h (2 days) before each admission to the study site until discharge;
- Normal 12-lead ECG findings as judged by the Investigator at screening and check-in, and evidenced by each criterion listed below:
- Normal sinus rhythm (heart rate between 50 bpm and 100 bpm, inclusive);
- Fridericia-corrected QTc (QTcF) interval ≤450 msec;
- QRS interval ≤120 msec, and confirmed by manual over read if >120 msec;
- PR interval ≤220 msec
- Good physical and mental health as judged by the Investigator and determined by medical and surgical history, physical examination, vital signs, or laboratory tests performed within 28 days before first study drug administration; For female subjects, physical examination must include breast examination and gynecological examination including a transvaginal ultrasound (TVUS) and a cervical (Papanicolaou [Pap]) smear if subject has not undergone one in the previous 18 months;
- Women of child-bearing potential and fertile male subjects with a sexual partner of other sex must be willing to use an adequate double-barrier contraception method from screening until 4 weeks after the last dose of study treatment;
- Capable and willing to give written informed consent (IC);
- Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions;
- Venous access sufficient to allow blood sampling as per protocol.
Exclusion Criteria:
- Renal insufficiency as determined by glomerular filtration rate [GFR] <60 mL/min/1.73 m2;
- History or presence of liver tumors, liver disease or liver injury as indicated by abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase (AST) >2x upper limit of normal (ULN) and bilirubin >1.5 ULN]. Any single parameter elevated >1.5-fold ULN should be re-checked once prior to enrollment/randomization;
- Pregnant or breast-feeding women;
- Menopausal and post-menopausal women. Menopause is defined as at least 12 months of spontaneous amenorrhea without another medical cause;
Use of estrogen or progestin-containing drug(s). A washout period is required before screening in case of use of:
- vaginal hormonal products (rings, creams, gels): washout of at least 4 weeks;
- transdermal estrogen or estrogen/progestin: washout of at least 4 weeks;
- oral estrogen and/or progestin: washout of at least 4 weeks;
- intrauterine progestin therapy: washout of at least 4 weeks;
- progestin implants or estrogen alone injectable drug therapy: washout of at least 3 months;
- estrogen pellet therapy or progestin injectable drug therapy: washout of at least 6 months.
- Women who have any clinically significant findings found by the Investigator at the breast examination and/or on mammography/ultrasound (performed only if deemed necessary by the Investigator) suspicious of breast malignancy (however, simple cysts confirmed by ultrasound are allowed);
- Women who have a Pap test with atypical squamous cells of undetermined significance (ASC-US or class II) or higher (low-grade squamous intraepithelial lesion [LSIL],] or class III and higher, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion [HSIL] [ASC-H], HSIL, dysplastic or malignant cells). Note: ASC-US or class II is allowed if a reflex human papilloma virus (HPV) testing is performed and is negative for high risk oncogene HPV;
- History of venous or arterial thromboembolic disease (e.g., superficial or deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, angina pectoris, etc.), or first-degree family history of venous thromboembolism (VTE);
- History of known acquired or congenital coagulopathy or abnormal coagulation factors, including known thrombophilia;
- Medical history or condition that, in the opinion of the Investigator, would preclude safe study participation or interfere with study procedures/assessments (e.g., unstable cardiovascular disease, type I or type II diabetes, major psychiatric disorder, seizures, porphyria, systemic lupus erythematosus, relevant gynecological pathology,…);
For non-hysterectomized subjects:
- history or presence of uterine cancer, endometrial hyperplasia, disordered proliferative findings; or
- presence of endometrial polyps; or
- undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding within the last 6 months; or
- endometrial ablation; or
- any uterine/endometrial abnormality that, in the judgment of the Investigator, contraindicates the use of estrogen therapy. This includes presence or history of adenomyosis or significant myoma
- Subjects who have inadequately treated hyperthyroidism with abnormal thyroid stimulating hormone (TSH) and free thyroxine (fT4) at screening. Subjects with low TSH are allowed if fT4 at screening is within normal range;
- Subjects who have laboratory values of fasting glucose above 125 mg/dL (>6.94 mmol/L) and/or glycated hemoglobin above 7%;
- Vital sign abnormalities (systolic BP lower than 90 or over 150 mmHg, diastolic BP lower than 40 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening;
- Subjects who have dyslipoproteinemia (low density lipoprotein [LDL] >190 mg/dL [>4.91 mmol/L] and/or triglycerides >300 mg/dL [>3.39 mmol/L]);
- Subjects taking prescription drugs, over-the-counter (OTC) medication, dietary supplements (vitamins included) or herbal remedies within 14 days prior to the first study dose, except for paracetamol with a maximum of 1 g/dose and maximum 3 g/day with minimum dose interval of 6 h.
- Subjects receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination within 7 days prior to the first study medication dose;
- Male subjects currently receiving estrogen-based hormonal therapy;
- Male subjects >50 years of age with prostate specific antigen (PSA) ≥ 4.0 ng/mL. Documented PSA testing results obtained within 1 year of screening are acceptable;
- Male subjects with prostate hyperplasia or micturition problems that suggest the presence of prostate hyperplasia;
- Positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (Ab-HCV) at screening or baseline;
- Positive human immunodeficiency virus (HIV) screen and/or a history of acquired immune deficiency syndrome (AIDS);
- Positive test result for SARS-CoV-2 at screening or baseline;
- Subjects who have a history of clinically serious arrhythmia or risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia;
- History or presence of allergy/intolerance to the IMP or drugs of this class or any component of it, or history of drug or other allergy that, in the opinion of the Investigator, contraindicates subject participation;
- History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit as determined by the Investigator, based on reported observations. Alcohol abuse is defined as use of >14 units per week for females (one unit of alcohol is equal to 250 mL beer [5 %] or 100 mL wine [12 %] or spirits [42.5 g of 40 % volume spirit]);
- History of significant drug abuse within 1 year prior to screening or use of soft drugs (such as marijuana, even if legally allowed) within 3 months prior to the screening visit, or hard drugs (such as cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
- Positive drug screen (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) at screening or baseline;
- Subjects who are currently participating in, or have participated in an investigational trial within 30 days prior to screening;
- Subjects who are Sponsor or Clinical Research Organization (CRO) employees or employees under the direct supervision of the Investigator and/or involved directly in the trial;
Donation or loss of
- ≥ 450 mL blood within 1 month prior to initial study drug administration;
- ≥ 250 mL blood within 2 weeks prior to initial study drug administration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
Cohort A: Single dose of placebo (n=2); Cohort B: Single dose of placebo (n=2); Cohort C: multiple dose of placebo (n=4) |
EXPERIMENTAL: Cohort A
|
Administration of a single intravenous (i.v.) infusion of estetrol (E4) 30 mg (n=6)
|
EXPERIMENTAL: Cohort B
|
Administration of a single i.v.
infusion of E4 100 mg (n=6)
|
EXPERIMENTAL: Cohort C
|
Administration of an i.v.
infusion of E4 100 mg (or lower dose, depending on single dose results) once a day for 5 consecutive days (n=8)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of treatment-emergent adverse events (TEAEs) - Cohort A and B
Time Frame: From Day 1 to End of Study (EoS) (Day 8)/ Early termination (ET)
|
From Day 1 to End of Study (EoS) (Day 8)/ Early termination (ET)
|
Number of treatment-emergent adverse events (TEAEs) - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Number of serious adverse events (SAEs) - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Number of serious adverse events (SAEs) - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: hemoglobin - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: hemoglobin - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: hematocrit - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: hematocrit - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: red blood cells - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: red blood cells - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular volume - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular volume - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin concentration - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin concentration - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: differential white blood cells - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: differential white blood cells - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hematology: thrombocytes - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hematology: thrombocytes - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: urea - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: urea - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: sodium - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: sodium - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: potassium - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: potassium - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: chloride - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: chloride - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: calcium - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: calcium - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: phosphate - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: phosphate - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: creatinine - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: creatinine - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: albumin - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: albumin - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: magnesium - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: magnesium - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: total protein - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: total protein - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: biochemistry: lactate dehydrogenase - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: biochemistry: lactate dehydrogenase - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: urinalysis: pH - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: urinalysis: pH - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: urinalysis: glucose - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: urinalysis: glucose - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: urinalysis: protein - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: urinalysis: protein - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: urinalysis: white blood cells - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: urinalysis: white blood cells - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: urinalysis: blood - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: urinalysis: blood - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Change from baseline in laboratory safety tests: hemostasis: prothrombin time - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
Change from baseline in laboratory safety tests: hemostasis: prothrombin time - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Observed maximum concentration (Cmax) of E4 and its metabolites (C3- and C16-glucuronides) -Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Observed maximum concentration (Cmax) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Time of Cmax (Tmax) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Time of Cmax (Tmax) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1(pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1(pre-infusion, i.e just prior dosing) to Day 9
|
|
Terminal phase half-life (T1/2) of E4 and its metabolites (C3- and C16-glucuronides) -Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Terminal phase half-life (T1/2) of E4 and its metabolites (C3- and C16-glucuronides) -Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Area under the curve from time zero (t0) to the last determined concentration (AUC0-t) of E4 and its metabolites (C3- and C16-glucuronides) -Cohort A and B
Time Frame: From Day 1(pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1(pre-infusion, i.e just prior dosing) to Day 5
|
|
Area under the curve from time zero (t0) to the last determined concentration (AUC0-t) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Area under the curve from t0 up to 24 hours after the beginning of drug infusion (AUC0-24) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Area under the curve from t0 up to 24 hours after the beginning of drug infusion (AUC0-24) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Area under the curve from t0 to infinity (AUC0-∞) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Area under the curve from t0 to infinity (AUC0-∞) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Clearance of E4 -Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
Volume of distribution (Vz) of E4 -Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Volume of distribution (Vz) of E4 -Cohort A and B
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
|
|
CL of E4 -Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Trough concentration level (Ctrough) of E4 and its metabolites (C3- and C16-glucuronides) - Cohort C
Time Frame: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
|
|
Effect of a single infusion of E4 30 mg and E4 100 mg on heart rate (HR): change-from-baseline heart rate (ΔHR)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on heart rate (HR): change-from-baseline heart rate (ΔHR)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on heart rate (HR): placebo-corrected change-from-baseline heart rate (ΔΔHR)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on heart rate (HR): placebo-corrected change-from-baseline heart rate (ΔΔHR)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on PR interval: change-from-baseline PR interval (ΔPR)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on PR interval: change-from-baseline PR interval (ΔPR)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on PR interval: placebo-corrected change-from-baseline PR interval (ΔΔPR)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on PR interval: placebo-corrected change-from-baseline PR interval (ΔΔPR)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on QRS interval: change-from-baseline QRS interval (ΔQRS)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on QRS interval: change-from-baseline QRS interval (ΔQRS)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on QRS interval: placebo-corrected change-from-baseline QRS interval (ΔΔQRS)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on QRS interval: placebo-corrected change-from-baseline QRS interval (ΔΔQRS)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on QTcF interval: change-from-baseline QTcF interval (ΔQTcF)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on QTcF interval: change-from-baseline QTcF interval (ΔQTcF)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Effect of a single infusion of E4 30 mg and E4 100 mg on QTcF interval: placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Time Frame: From 1 hour pre-infusion to 24 hours post-infusion
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion to 24 hours post-infusion
|
Effect of a daily infusion of E4 100 mg for 5 consecutive days on QTcF interval: placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Time Frame: From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Continuous 12-lead ECG (Holters) recordings will be performed.
|
From 1 hour pre-infusion on Day 1 and on Day 5 to 24 hours post-infusion (i.e. Day 2 and Day 6)
|
Frequency of treatment emergent changes of T-wave morphology and U-wave presence - Cohort A and B
Time Frame: From Day 1 to EoS (Day 8)/ ET
|
From Day 1 to EoS (Day 8)/ ET
|
|
Frequency of treatment emergent changes of T-wave morphology and U-wave presence - Cohort C
Time Frame: From Day 1 to EoS (Day 29+7) / ET
|
From Day 1 to EoS (Day 29+7) / ET
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- MIT-Ne001-C101
- 2021-003781-12 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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