A Study With an Open-Label Active Control to Evaluate the Potential of Nestorone® to Delay Cardiac Repolarization in Healthy Female Volunteers

NCT02236026 | Completed Phase 1

• 1 other identifier: 648
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the effect of Nestorone (NES) administered as an bolus injection on the corrected QT interval using Fridericia's formula (QTcF).

Conditions

Healthy

Keywords

Nestorone use as an IV solution on heart rate;; Abnormality in Heart Rate or Rhythm, Unspecified as to Time of Onset

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of Nestorone (NES) administered as an IV solution on the corrected QT interval using Fridericia's formula (QTcF).

  Measurement of any changes from baseline in heart rhythm using an electrocardiogram at different time points after receiving NES as an IV solution

  Days 1, 2, 30, 31, 32, and 33

Study Arms (3)

Supratherapeutic dose of Nestorone

EXPERIMENTAL

Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor

Drug: Supratherapuetic dose of Nestorone

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor

Drug: Placebo

Moxifloxacin

EXPERIMENTAL

Subjects will be randomized to a treatment sequence on Day 1 of Treatment Period 1, prior to administration of investigational product, according to a randomization schedule provided by the Sponsor

Drug: Moxifloxacin

Interventions

Supratherapuetic dose of Nestorone DRUG

Supratherapeutic dose of Nestorone

Placebo DRUG

Placebo

Moxifloxacin DRUG

Moxifloxacin

Eligibility Criteria

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

You may qualify if:

• Is a premenopausal female, ≥ 18 to \< 40 years of age at the time of Screening;
• Has a BMI ≥ 18.5 and ≤ 32 kg/m2 (weight ≥ 50 kg) at Screening
• Is in a state of general good health based on medical history and physical examination;
• Is regularly menstruating (cycles of 22 to 35 days duration) over the previous 6 months prior to Screening, as reported by the subject;
• If of childbearing potential, must be practicing an acceptable non-hormonal, method of birth control until the end of the study (Exit/Early Termination). Such methods include but are not limited to: Sexual abstinence; Male or female condom in combination with spermicidal foam/gel/cream/ suppository; Vasectomized or female partner; Diaphragm/cervical cap with spermicide; Bilateral tubal ligation sterilization at least 6 months before the screening visit, or an ESSURE or ADIANA procedure with an hysterosalpingography confirmation test at least 6 months before the screening visit; Copper intrauterine device.
• Is able to fulfill the requirements of the protocol, and indicates a willingness to participate in the study by providing written informed consent and an authorization to disclose PHI.

You may not qualify if:

• Is pregnant or lactating;
• Has hypersensitivity or allergy to NES, moxifloxacin, or related compounds, or any of the inactive ingredients used in the investigational product formulations;
• Has a contraindication to progestin or estrogen therapy;
• Has impaired hypothalamic-pituitary-adrenal reserve, or history of oral glucocorticoid replacement therapy in 12 months prior to Screening.
• Has experienced undiagnosed genital bleeding, excluding inter-menstrual spotting, within 6 months of Screening;
• Has undergone a gynecological examination, which results in clinically significant abnormalities, at Screening;
• Has had treatment with oral, topical or vaginal steroid hormones (e.g., estrogens, progestogens, androgens \[including dehydroepiandrosterone\], corticosteroids) within 8 weeks prior to Screening, or treatment with injectable or implantable steroids at any time during the 6 months prior to Screening;
• Is currently using, or has used within 6 months prior to Screening, hormonal contraception or progestin intrauterine device.
• Has known or suspected carcinoma of the breast;
• Has benign or malignant liver tumors or acute liver disease;
• Has current or past thrombophlebitis or thromboembolic disorders or a family history of thromboembolic disorders;
• Has a personal history of myocardial disease, Long QT Syndrome or a personal or family history of Long QT Syndrome (e.g., Anderson-Tawil Syndrome \[micrognathia, low set ears, clinodactyly\]; Timothy's Syndrome \[syndactyly and autism spectrum disorder\];: Jervell/Lange-Nielsen Syndrome \[bilateral hearing loss\]; Romano-Ward Syndrome \[fainting, seizures\]), unexplained syncope or presyncope, or current or recurrent hypokalemia.
• Has a family history in genetically related grandparents, parents, uncles/aunts, cousins, or children of Long QT Syndrome, non-ischemic cardiomyopathy, or unexplained sudden death before 50 years of age.
• Has an abnormal 12-lead ECG, with clinically significant abnormalities of rate, rhythm, or conduction including: HR \< 45 or \> 90 beats per minute (bpm), after a 5 minute supine rest; PR interval \> 220 ms; QRS interval \> 120 ms; QTcF or corrected QT interval using Bazett's formula (to be determined by Investigator) \> 450 ms; QTcF \< 300 ms; Any degree of clinically significant fascicular block, bundle branch block, or intraventricular conduction delay; QRS and/or T wave that the Investigator judges to be unfavorable for consistently accurate QT measurements (e.g., indistinct QRS onset, low amplitude T wave, inverted or terminally inverted T wave, merged T/U waves, indistinct T wave offset, or prominent U wave that affects QT measurement); Neuromuscular artifact that cannot be readily eliminated;
• Has, on ECG, premature atrial or ventricular beats or other findings that in the Investigator's opinion represent clinically significant excessive HR variation;

Sponsors & Collaborators

• Population Council: lead
• Parexel: collaborator

Study Sites (1)

Harbor Hospital, 3001 South Hanover Street, 7th Floor

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• George W. Creasy, MD

  Population Council

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 10, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 15, 2017

Record last verified: 2017-08

Locations

US (1)