SafetyPhase 1NCT05460065
Single and Multiple Intravenous Administrations of Estetrol (E4) in Healthy Adult Volunteers
A Phase 1 study testing single E4 28.3 mg, single E4 94.4 mg and multiple E4 94.4 mg in people with Safety and Pharmacokinetics, run by NEURALIS s.a. at 1 site in Bulgaria.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety, Pharmacokinetics
- What is being tested?
- single E4 28.3 mg, single E4 94.4 mg and multiple E4 94.4 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteBulgaria
- Study dates
- 19 Apr 2022to 13 Sep 2022
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
The study will be conducted in a dose escalation design, starting with a single dose of 28.3 mg (Cohort A). After completion of the treatment period of the cohort, a review of the safety and tolerability data will be performed by a blinded dose-escalation safety review team (DESRT) consisting of medical and research experts of the Sponsor and CRO, and the principal investigator. If this review is satisfactory, the study will be continued with a next cohort of volunteers who will receive a higher single dose of 94.4 mg (Cohort B). A safety review will be applied again for moving from the single dose Cohort B to the multiple dose cohort (Cohort C). At this stage, the safety review team may decide to reduce the daily dose to be used for the multiple dose cohort from what is initially proposed in the protocol.
- Conditions
- Safety, Pharmacokinetics
- Being tested
- single E4 28.3 mg, single E4 94.4 mg, multiple E4 94.4 mg, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
single E4 28.3 mgDrug
Administration of a single intravenous (i.v.) infusion of estetrol (E4) 28.3 mg (n=6)
single E4 94.4 mgDrug
Administration of a single i.v. infusion of E4 94.4 mg (n=6)
multiple E4 94.4 mgDrug
Administration of an i.v. infusion of E4 94.4 mg (or lower dose, depending on single dose results) once a day for 5 consecutive days (n=8)
PlaceboDrug
Cohort A: Single dose of placebo (n=2);
Cohort B: Single dose of placebo (n=2);
Cohort C: multiple dose of placebo (n=4)
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Not described Receives: Drug: single E4 28.3 mg |
| Cohort B | Experimental | Not described Receives: Drug: single E4 94.4 mg |
| Cohort C | Experimental | Not described Receives: Drug: multiple E4 94.4 mg |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of treatment-emergent adverse events (TEAEs) - Cohort A and B
Measured: From Day 1 to End of Study (EoS) (Day 8)/ Early termination (ET)
Number of treatment-emergent adverse events (TEAEs) - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Number of serious adverse events (SAEs) - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Number of serious adverse events (SAEs) - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: hemoglobin - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: hemoglobin - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: hematocrit - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: hematocrit - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: red blood cells - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: red blood cells - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: mean corpuscular volume - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: mean corpuscular volume - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin - Cohort C
Measured: 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
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin concentration - Cohort C
Measured: 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
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: differential white blood cells - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hematology: thrombocytes - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hematology: thrombocytes - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: urea - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: urea - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: sodium - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: sodium - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: potassium - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: potassium - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: chloride - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: chloride - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: calcium - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: calcium - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: phosphate - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: phosphate - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: creatinine - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: creatinine - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: albumin - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: albumin - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: magnesium - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: magnesium - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: total protein - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: total protein - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: biochemistry: lactate dehydrogenase - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: biochemistry: lactate dehydrogenase - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: urinalysis: pH - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: urinalysis: pH - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: urinalysis: glucose - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: urinalysis: glucose - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: urinalysis: protein - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: urinalysis: protein - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: urinalysis: white blood cells - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: urinalysis: white blood cells - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: urinalysis: blood - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: urinalysis: blood - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Change from baseline in laboratory safety tests: hemostasis: prothrombin time - Cohort A and B
Measured: From Day 1 to EoS (Day 8)/ ET
Change from baseline in laboratory safety tests: hemostasis: prothrombin time - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Secondary outcomes (35)
Observed maximum concentration (Cmax) of E4 and its metabolites (C3- and C16-glucuronides) -Cohort A and B
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
Clearance of E4 -Cohort A and B
Measured: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
Volume of distribution (Vz) of E4 -Cohort C
Measured: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
Volume of distribution (Vz) of E4 -Cohort A and B
Measured: From Day 1 (pre-infusion, i.e just prior dosing) to Day 5
CL of E4 -Cohort C
Measured: 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
Measured: From Day 1 (pre-infusion, i.e just prior dosing) to Day 9
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on heart rate (HR): change-from-baseline heart rate (ΔHR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on heart rate (HR): change-from-baseline heart rate (ΔHR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on heart rate (HR): placebo-corrected change-from-baseline heart rate (ΔΔHR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on heart rate (HR): placebo-corrected change-from-baseline heart rate (ΔΔHR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on PR interval: change-from-baseline PR interval (ΔPR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on PR interval: change-from-baseline PR interval (ΔPR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on PR interval: placebo-corrected change-from-baseline PR interval (ΔΔPR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on PR interval: placebo-corrected change-from-baseline PR interval (ΔΔPR)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on QRS interval: change-from-baseline QRS interval (ΔQRS)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on QRS interval: change-from-baseline QRS interval (ΔQRS)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on QRS interval: placebo-corrected change-from-baseline QRS interval (ΔΔQRS)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on QRS interval: placebo-corrected change-from-baseline QRS interval (ΔΔQRS)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on QTcF interval: change-from-baseline QTcF interval (ΔQTcF)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on QTcF interval: change-from-baseline QTcF interval (ΔQTcF)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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 28.3 mg and E4 94.4 mg on QTcF interval: placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 mg for 5 consecutive days on QTcF interval: placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Continuous 12-lead ECG (Holters) recordings will be performed.
Measured: 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
Measured: From Day 1 to EoS (Day 8)/ ET
Frequency of treatment emergent changes of T-wave morphology and U-wave presence - Cohort C
Measured: From Day 1 to EoS (Day 29+7) / ET
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2022
- Study start19 Apr 2022
- Primary completion13 Sep 2022
- Study completion13 Sep 2022
Why it stopped: Business decision by Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SafetyStudies 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
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- NEURALIS s.a.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05460065
- Sponsor's protocol ID
- MIT-Ne001-C101
- Other IDs
- 2021-003781-12
- Status last verified
- Jul 2025
- First submitted
- 25 Mar 2022
- Last updated
- 4 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05460065
- Acronym / sponsor ID
- MIT-Ne001-C101
- Conditions
- Safety, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision by Sponsor.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- NEURALIS s.a.Industry (pharma, biotech, devices)
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 13 Sep 2022 (actual)
- Study completion
- 13 Sep 2022 (actual)
- First posted
- 15 Jul 2022 (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.
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.
Detailed description
The study will be conducted in a dose escalation design, starting with a single dose of 28.3 mg (Cohort A). After completion of the treatment period of the cohort, a review of the safety and tolerability data will be performed by a blinded dose-escalation safety review team (DESRT) consisting of medical and research experts of the Sponsor and CRO, and the principal investigator. If this review is satisfactory, the study will be continued with a next cohort of volunteers who will receive a higher single dose of 94.4 mg (Cohort B). A safety review will be applied again for moving from the single dose Cohort B to the multiple dose cohort (Cohort C). At this stage, the safety review team may decide to reduce the daily dose to be used for the multiple dose cohort from what is initially proposed in the protocol.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: single E4 28.3 mg |
| Cohort B | Experimental | Drug: single E4 94.4 mg |
| Cohort C | Experimental | Drug: multiple E4 94.4 mg |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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;
Key exclusion criteria (44 listed)
- 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:
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 |
|---|---|---|
| single E4 28.3 mgAdministration of a single intravenous (i.v.) infusion of estetrol (E4) 28.3 mg (n=6) | Drug | Cohort A |
| single E4 94.4 mgAdministration of a single i.v. infusion of E4 94.4 mg (n=6) | Drug | Cohort B |
| multiple E4 94.4 mgAdministration of an i.v. infusion of E4 94.4 mg (or lower dose, depending on single dose results) once a day for 5 consecutive days (n=8) | Drug | Cohort C |
| PlaceboCohort A: Single dose of placebo (n=2); Cohort B: Single dose of placebo (n=2); Cohort C: multiple dose of placebo (n=4) | Drug | Placebo |
Primary outcome
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)
Number of treatment-emergent adverse events (TEAEs) - Cohort C
Time frame: 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
Number of serious adverse events (SAEs) - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hematology: hemoglobin - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hematology: hematocrit - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hematology: red blood cells - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hematology: mean corpuscular volume - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hematology: mean corpuscular hemoglobin - Cohort C
Time frame: 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
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
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
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
Change from baseline in laboratory safety tests: hematology: thrombocytes - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: urea - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: sodium - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: potassium - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: chloride - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: calcium - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: phosphate - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: creatinine - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: albumin - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: magnesium - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: total protein - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: biochemistry: lactate dehydrogenase - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: urinalysis: pH - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: urinalysis: glucose - Cohort A and B
Time frame: 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
Change from baseline in laboratory safety tests: urinalysis: protein - Cohort A and B
Time frame: 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
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
Change from baseline in laboratory safety tests: urinalysis: white blood cells - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: urinalysis: blood - Cohort C
Time frame: 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
Change from baseline in laboratory safety tests: hemostasis: prothrombin time - Cohort C
Time frame: From Day 1 to EoS (Day 29+7) / ET
35 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
Clearance of E4 -Cohort A and B
Time frame: 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
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
CL of E4 -Cohort C
Time frame: 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
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on heart rate (HR): change-from-baseline heart rate (ΔHR)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 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
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on PR interval: change-from-baseline PR interval (ΔPR)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on PR interval: placebo-corrected change-from-baseline PR interval (ΔΔPR)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on QRS interval: change-from-baseline QRS interval (ΔQRS)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on QRS interval: placebo-corrected change-from-baseline QRS interval (ΔΔQRS)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on QTcF interval: change-from-baseline QTcF interval (ΔQTcF)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
Effect of a single infusion of E4 28.3 mg and E4 94.4 mg on QTcF interval: placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Time frame: From 1 hour pre-infusion to 24 hours post-infusion
Effect of a daily infusion of E4 94.4 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)
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
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
Results and safety
The study was stopped early (reason given: Business decision by Sponsor.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2025.
- Individual participant dataSharing planned: Undecided
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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 single E4 28.3 mg, single E4 94.4 mg and multiple E4 94.4 mg in people with Safety and Pharmacokinetics, run by NEURALIS s.a. at 1 site in Bulgaria.
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 15 inclusion and 44 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 4 Jul 2025. 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 Bulgaria. 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. Some participants in this study may receive a placebo. 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: Business decision by Sponsor.). 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?
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)). The study lists 54 primary outcomes in all. 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 4 Jul 2025.