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Infections, BacterialPhase 1NCT01953809

A Pharmacokinetics, Pharmacodynamics, and Safety Study of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol When Co-administered With GSK1322322 in Healthy Adult Women

A Phase 1 study testing GSK1322322 and EE/NE in people with Infections, Bacterial, run by GlaxoSmithKline.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study is being conducted to confirm that GSK1322322 has no negative impact on hormone levels and contraceptive efficacy when co-administered with a frequently prescribed oral contraceptive thereby to facilitate the use of GSK1322322 in women of child-bearing potential receiving oral contraceptive (OC)… Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Infections, Bacterial
What is being tested?
GSK1322322 and EE/NE
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2014to Mar 2015
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 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Non smoking female (of childbearing age), between 18 and 45 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy without oophorectomy (at least one functioning ovary required) or child bearing age with the presence of non-drug eluting intra uterine device (IUD) i.e. copper. NOTE: The IUD placement needs to be confirmed by an obstetrician-gynecologist.
  • Subjects must be willing to use EE/NE in combination with one of the following appropriate contraceptive methods from at least 14 days prior to the first dose of study drug until completion of the follow-up visit Complete abstinence from intercourse for at least 14 days prior to the first dose of IP, throughout the study, and for the subsequent post study monitoring or; A barrier method plus a spermicide (e.g., condom or diaphragm with spermicidal foam/gel/cream/ suppository for at least 14 days prior to the first dose of IP throughout the study, and for the subsequent post study monitoring or Sterilization (vasectomy) of male partner prior to commencement of female subject's last normal menstrual period prior to IP administration and the male partner is the sole partner for that female subject
  • Body weight >=50 kilograms (kg) (110 pounds [lbs]) and <114kg (<250 lbs) and body mass index within the range 19 to 32 kg/meter^2 (inclusive).
  • Alanine aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening and check-in (repeat allowed at check-in only).
  • QT interval corrected for heart rate by Bazett's formula (QTcB) < 450 millisecond (msec) at screening and check-in.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Who cannot join

  • Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at screening or prior to dosing.
  • History of any condition that would contraindicate Ortho-Novum administration (including hypertension, stroke, ischemic heart disease, venous thromboembolism or family history of thromboembolism, known factor V Leiden mutation or other gene mutations associated with increased risk of thromboembolism, migraine headaches, carcinoma of the breast, liver or endometrium, gallbladder disease, history of undiagnosed abnormal uterine bleeding, etc.
  • Females with conditions or concurrent medications that could adversely affect hormone levels (e.g. oophorectomies).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Endocrine system: untreated or unstable thyroid disorder and/or diabetes mellitus (I and II). Treatment of the condition must be stable for at least 4 weeks prior to first dose of study drug.
  • Have suffered a urinary tract, bladder, or vaginal infection within 4 weeks prior to the first dose of study drug, or has a urinalysis result at Screening consistent with an urinary tract infection. Subjects diagnosed with an infection at Screening should be treated appropriately and may be re-screened after 4 weeks.
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  • Fasting triglycerides > 300 mg/deciliter (dL) at Screening.
  • A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or a positive test for human immuno virus (HIV) antibody result within 3 months of screening.
  • A positive pre-study drug/alcohol screen.
  • History of regular alcohol consumption within 6 months of the study defined as An average weekly intake of >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • Concurrent-medications that alter gastro-intestinal motility result in diarrhea or bind study drugs (for example erythromycin, antacids, prokinetic agents, cholestyramine).
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety due to potential drug interaction.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Lactating females.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Urinary cotinine levels indicative of smoking or regular use of tobacco- or nicotine-containing products within 4 weeks prior to screening.
  • Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):
  • Female subjects with Heart rate <50 and >100 beats per minute (bpm), PR interval <120 and >220 msec, QRS duration <70 and >120 msec, QTcB >=450 msec (Note: The waveforms must enable the QT interval to be clearly defined), Q wave>30 msec Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization).
  • Any conduction abnormality (including but not specific to left or right bundle branch block, AV block (2nd degree or higher), Wolf Parkinson White (WPW) syndrome), sinus pauses> 3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.

About this study

Official title: A Phase 1, Randomized, Single Blind Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol When Co-administered With GSK1322322 in Healthy Adult Women of Childbearing Age Who Are of Non-Childbearing Potential Due to Surgical Sterilization or IUD Placement (PDF112163)

This study is being conducted to confirm that GSK1322322 has no negative impact on hormone levels and contraceptive efficacy when co-administered with a frequently prescribed oral contraceptive thereby to facilitate the use of GSK1322322 in women of child-bearing potential receiving oral contraceptive (OC) pre-infection. This study is designed to investigate steady-state plasma ethinyl estradiol (EE) and norethindrone (NE) pharmacokinetic (PK) following administration of Ortho-Novum (EE/NE) 1 tablet every 24 hours (q24h) fed with and without GSK1322322 1500 milligram (mg) q12h fed. Each subject will participate in the study for approximately 12 weeks: a 30 day screening period, 4-week run-in period, three 7 day treatment periods, and a 3-5 day follow-up period. The study is planned to enroll approximately 24 subjects (18 active/6 placebo).

Read the detailed description

Please note that Ortho-Novum is a registered trademark of Ortho Pharmaceutical Corporation.

Being tested
GSK1322322, EE/NE, GSK1322322 Placebo, EE/NE Placebo
Keywords
oral, oral contraceptive, pharmacokinetics, drug interaction, pharmacodynamics, GSK1322322, antibiotic, safety
Medical subject headings
Bacterial Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1322322Drug

    Oral tablets with unit dose strength of 500mg and dose level of 1500mg (3 x 500mg) for twice a day administration for 7 days in treatment phase

  • EE/NEDrug

    Oral contraceptive tablet containing 0.035mg EE and 1mg NE for once daily administration for 21 days in run-in phase and 21 days in treatment phase

  • GSK1322322 PlaceboDrug

    GSK1322322 matching placebo tablets for twice a day administration (3 tablets each time) for 7 days in treatment period.

  • EE/NE PlaceboDrug

    EE/NE matching placebo tablet for once daily administration for 7 days in run-in phase.

Study groups in NCT01953809
Study groupRoleWhat they receive
Run-in PeriodExperimentalAll subjects will receive EE/NE for first 21 days and EE/NE matching placebo for next 7 days before start of treatment phase
Receives: Drug: EE/NE; Drug: EE/NE Placebo
Group 1ExperimentalSubjects upon completion of 28 days of run-in period will receive GSK1322322/Placebo + EE/NE in period 1 and only EE/NE in period 2 and 3 of treatment phase. Each period will be of 7 days
Receives: Drug: GSK1322322; Drug: EE/NE; Drug: GSK1322322 Placebo
Group 2ExperimentalSubjects upon completion of 28 days of run-in period will receive only EE/NE in period 1, GSK1322322/Placebo + EE/NE in period 2 and again EE/NE only in period 3 of treatment phase. Each period will be of 7 days
Receives: Drug: GSK1322322; Drug: EE/NE; Drug: GSK1322322 Placebo
Group 3ExperimentalSubjects upon completion of 28 days of run-in period will receive only OC in period 1 and 2, and GSK1322322/Placebo + EE/NE in period 3 of treatment phase. Each period will be of 7 days
Receives: Drug: GSK1322322; Drug: EE/NE; Drug: GSK1322322 Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of PK parameters of EE/NE to compare the steady state plasma PK. If data permit, after EE/NE alone for 7 days and after EE/NE with GSK1322322 for 7 days.

    PK parameters include: steady-state area under the concentration-time curve over the dosing interval (AUC[0-tau]), maximum observed concentration (Cmax), time of occurrence of Cmax (Tmax), minimum observed concentration (Cmin), and terminal phase half-life (t1/2)

    Measured: Plasma PK samples will be collected at pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours on Day 7, 14 and 21 of both run-in phase and on treatment phase.

Secondary outcomes (9)
  1. Composite of PK parameters of GSK1322322 following co-administration of GSK1322322 and EE/NE for 7 days

    PK parameters include: steady-state AUC(0-tau), Cmax, Tmax

    Measured: Plasma PK samples will be collected at pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on day 7, 14, and 21 of treatment phase.

  2. Number of subjects with adverse events (AEs) as a measure of safety and tolerability

    AEs will be collected from the start of Study Treatment and until the follow-up contact.

    Measured: 8 weeks

  3. Concurrent medication assessment as a measure of safety and tolerability

    Measured: 8 weeks

  4. Laboratory parameter assessment as a measure of safety and tolerability

    Laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters

    Measured: 8 weeks

  5. Electrocardiogram (ECG) assessment as a measure of safety and tolerability.

    12-lead ECGs will be obtained at each time point using an ECG machine that automatically to calculate the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate

    Measured: 8 weeks

  6. Vital sign measurement as a measure of safety and tolerability

    Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate

    Measured: 8 weeks

  7. Pre-dose serum level of Lutenizing Hormone (LH).

    LH will be evaluated as surrogate marker of contraceptive efficacy

    Measured: 7 weeks

  8. Pre-dose serum level of Follicle stimulating hormone (FSH)

    FSH will be evaluated as surrogate marker of contraceptive efficacy

    Measured: 7 weeks

  9. Pre-dose serum level of Progesterone

    Progesterone will be evaluated as surrogate marker of contraceptive efficacy

    Measured: 7 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2013 (estimated)
  2. Study startAug 2014
  3. Primary completionMar 2015 (estimated)
  4. Study completionMar 2015 (estimated)

Why it stopped: Emerging GSK1322322 pre-clinical data ID'd potentially reactive metabolites previously not seen that changed the risk: benefit profile and led to a termination

Resources

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
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
Single blind
Who is masked
Participant
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01953809
Sponsor's protocol ID
112163
Status last verified
Jan 2015
First submitted
26 Sep 2013
Last updated
28 Jan 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1322322 and EE/NE in people with Infections, Bacterial, run by GlaxoSmithKline.

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 8 inclusion and 23 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: withdrawn, as of the sponsor's last update on 28 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 withdrawn before enrolling participants, so there are no results.

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?

Composite of PK parameters of EE/NE to compare the steady state plasma PK. If data permit, after EE/NE alone for 7 days and after EE/NE with GSK1322322 for 7 days. (time frame: Plasma PK samples will be collected at pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours on Day 7, 14 and 21 of both run-in phase and on treatment phase.). 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 28 Jan 2015.

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