Effect of Estetrol Monohydrate (E4) on QTc Interval

NCT04819906 | Completed Phase 1 FDA Drug

• 1 other identifier: MIT-Do001-C104
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

• to evaluate if E4 has any effect on how the heart beats when a single dose is given at two different dose levels;
• to determine the ability to detect small changes in how the heart beats using a positive control: moxifloxacin, a quinolone antibiotic approved by the FDA as a positive control in thorough QT (TQT) studies;
• to assess the safety and tolerability of a single dose of E4 administered at two different dose levels;
• to measure the amount of study drug in the blood stream and how long it takes for the body to eliminate it (Pharmacokinetics) after administration.

Conditions

Prolonged QTc Interval

Keywords

Estetrol; Moxifloxacin

Outcome Measures

Primary Outcomes (1)

• Effect of E4 20 mg and E4 100 mg on QTc interval: placebo-corrected change from baseline QTcF (ΔΔQTcF)

  Continuous 12-lead ECG (Holters) recordings will be performed. Baseline will be the average of the derived ECG intervals from the 3 predose ECG time points (-45, -30, and -15 minutes).

  from 45 minutes pre-dose to 24 hours post-dose

Secondary Outcomes (11)

• Effect of E4 20 mg and E4 100 mg on heart rate (HR): change-from-baseline heart rate (∆HR)

  from 45 minutes pre-dose to 24 hours post-dose

• Effect of E4 20 mg and E4 100 mg on heart rate (HR): placebo-corrected change-from-baseline heart rate (∆∆HR)

  from 45 minutes pre-dose to 24 hours post-dose

• Effect of E4 20 mg and E4 100 mg on PR interval: change-from-baseline PR interval (∆PR)

  from 45 minutes pre-dose to 24 hours post-dose

• Effect of E4 20 mg and E4 100 mg on PR interval: placebo-corrected change-from-baseline PR interval (∆∆PR)

  from 45 minutes pre-dose to 24 hours post-dose

• Effect of E4 20 mg and E4 100 mg on QRS duration: change-from-baseline QRS duration (∆QRS)

  from 45 minutes pre-dose to 24 hours post-dose

Study Arms (12)

T-ST-P-M

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

ST-M-T-P

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

P-T-M-ST

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

M-P-ST-T

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

ST-P-T-M

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

P-M-ST-T

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

T-ST-M-P

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

M-T-P-ST

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

P-T-ST-M

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

T-M-P-ST

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

ST-P-M-T

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

M-ST-T-P

EXPERIMENTAL

Treatment T: Therapeutic E4 dose (20 mg): one E4 20 mg tablet plus four E4 placebo tablets Treatment ST: Supratherapeutic E4 dose (100 mg): five E4 20 mg tablets Treatment P: Placebo: five E4 placebo tablets Treatment M: Moxifloxacin: 1 moxifloxacin 400 mg tablet

Drug: Estetrol 20 mg; Drug: Estetrol 100 mg; Drug: Placebo; Drug: Moxifloxacin 400 mg

Interventions

Estetrol 20 mg DRUG

One estetrol monohydrate (E4) 20 mg tablet plus four matching placebo tablets orally once

Also known as: E4 20 mg

M-P-ST-T; M-ST-T-P; M-T-P-ST; P-M-ST-T; P-T-M-ST; P-T-ST-M; ST-M-T-P; ST-P-M-T; ST-P-T-M; T-M-P-ST; T-ST-M-P; T-ST-P-M

Estetrol 100 mg DRUG

Five estetrol monohydrate (E4) 20 mg tablets orally once

Also known as: E4 100 mg

M-P-ST-T; M-ST-T-P; M-T-P-ST; P-M-ST-T; P-T-M-ST; P-T-ST-M; ST-M-T-P; ST-P-M-T; ST-P-T-M; T-M-P-ST; T-ST-M-P; T-ST-P-M

Placebo DRUG

Five placebo tablets orally once

M-P-ST-T; M-ST-T-P; M-T-P-ST; P-M-ST-T; P-T-M-ST; P-T-ST-M; ST-M-T-P; ST-P-M-T; ST-P-T-M; T-M-P-ST; T-ST-M-P; T-ST-P-M

Moxifloxacin 400 mg DRUG

One moxifloxacin 400 mg tablet orally once (open-label)

M-P-ST-T; M-ST-T-P; M-T-P-ST; P-M-ST-T; P-T-M-ST; P-T-ST-M; ST-M-T-P; ST-P-M-T; ST-P-T-M; T-M-P-ST; T-ST-M-P; T-ST-P-M

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, postmenopausal women, 40 years to 65 years of age, inclusive, at screening.
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose of study drug.
• Minimum weight of 52 kg and body mass index (BMI) ≥18.0 and ≤32.0 kg/m2 at screening.
• Healthy status defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination including gynecological examination, vital signs, a 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology, and urinalysis clinical laboratory tests.
• Postmenopausal status will be defined as any of the following:
• For non-hysterectomized participants:
• at least 12 months of spontaneous amenorrhea; or

You may not qualify if:

• at least 6 weeks postsurgical bilateral oophorectomy.
• For hysterectomized participants:
• at least 6 weeks postsurgical bilateral oophorectomy.
• Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol.
• Supine or semi-recumbent blood pressure between 90/40 mmHg and 150/90 mmHg (inclusive) at screening.
• No clinically significant history or presence of 12-lead ECG findings as judged by the Principal Investigator at screening and check-in, including each criterion as listed below:
• normal sinus rhythm (heart rate between 40 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.
• Has serum potassium, calcium, and magnesium levels within the normal range at screening.
• Ability and willingness to abstain from alcohol-, caffeine-, and xanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, energy drinks) from 48 hours (2 days) before each admission to the clinical research unit (CRU) until clinic discharge.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Principal Investigator.
• History of any illness that, in the opinion of the Principal Investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose of study drug.

Sponsors & Collaborators

• Estetra: lead

Study Sites (1)

QPS Miami

Miami, Florida, 33143, United States

Location

MeSH Terms

Interventions

Estetrol; Moxifloxacin

Intervention Hierarchy (Ancestors)

Estriol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 29, 2021
• Study Start: March 9, 2021
• Primary Completion: July 14, 2021
• Study Completion: July 14, 2021
• Last Updated: September 15, 2023

Record last verified: 2023-09

Locations

US (1)