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Postpartum HemorrhagePhase 1NCT02542813

Safety, Tolerability and Pharmacokinetics (PK) Study of Oxytocin (GR121619) Administered Via an Inhaled Route in Healthy Female Volunteers

A Phase 1 study testing IM oxytocin 10 IU, IH oxytocin 50 mcg and IH oxytocin 200 mcg in people with Postpartum Hemorrhage, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Intramuscular (IM) oxytocin is the gold standard prophylactic therapy for post partum haemorrhage (PPH). However, in resource-poor settings within the developing world, the stability and therefore effectiveness of prophylactic IM oxytocin is diminished by a lack of appropriate refrigeration facilities and availability… 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
Postpartum Hemorrhage
What is being tested?
IM oxytocin 10 IU, IH oxytocin 50 mcg and IH oxytocin 200 mcg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
1 siteUnited Kingdom
Study dates
14 Sep 2015to 16 Dec 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

  • Between 18 and 45 years of age inclusive, at the time of signing the informed consent.
  • Premenopausal women on an oestrogen-containing oral contraceptive pill (OCP) for a 12 month minimum period and to continue their current OCP schedule for the duration of the clinical study and until completion of the follow-up visit.
  • Physically capable of using an oral inhalation dry powder inhaler (DPI) device without physical assistance.
  • FEV1.0 within normal range at screening.
  • Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body mass index (BMI) within the range 18 - 30 kilogram (kg)/square meter (m^2) (inclusive).
  • Only females may participate. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: The investigator is responsible for ensuring that subjects are reminded during the study of the importance of maintaining compliance to oral contraception.
  • Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Who cannot join

  • Postmenopausal female as defined by gynaecological history.
  • Chronic lung condition of any aetiology including adult asthma, chronic obstructive pulmonary disease (COPD), emphysema and interstitial lung diseases.
  • Previous or current clinical history of proven pulmonary or systemic tuberculosis (TB).
  • Proven or suspected respiratory tract infection / pneumonia of any aetiology within 4 weeks of screening.
  • Current history of smoking and previous smokers within one year of the screening visit (if unsure about cessation of smoking status please refer to guidance below in "Relevant Habits".
  • History of pulmonary embolus, pulmonary hypertension of any aetiology, and peripheral venous thromboembolism.
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  • Average baseline systolic blood pressure (SBP) <=100 millimeter of mercury (mmHg) at three separate readings.
  • Use of an intrauterine device (IUD) within last 3 months.
  • Any pregnancy within last 12 months.
  • Gynaecological disorders or other diseases which can increase the risk of pelvic fibrosis are excluded, since acute uterine rupture after administration of oxytocin in postpartum women has been associated with a history of Caesarean section, possibly caused by intrauterine / pelvic scarring: a) Previous ectopic pregnancy, b) Previous pelvic, abdominal or lower spinal radiotherapy for any indication, c) Previous laparotomy for any abdominal or gynaecological indication, except no more than two previous caesarean-section(s), Previous gynaecological or urological history including endometrosis, adenomyosis, fibroids, or local bladder surgery.
  • ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Corrected QT interval using Fridericia's formula (QTcF) >450 millisecond (msec) (based on triplicate ECGs).
  • Prescription or non-prescription drugs not approved by the investigator, including vaginal prostaglandins within two weeks of dosing.
  • History of regular alcohol consumption within 6 months of the study defined as: For United Kingdom (UK) sites: an average weekly intake of >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History or regular use of tobacco- or nicotine-containing products within one year prior to screening. Confirmatory use via a Smokerlyzer is at the discretion of the local investigator, but is advised if the subject's recent smoking history is in doubt.
  • 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 Medical Monitor, contraindicates their participation such as - Allergy to latex; allergy to any previous inhaler use.
  • Positive pregnancy test at screening.
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • 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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Single Centre, Single Blind Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin (GR121619) Administered Via an Inhaled Route in Healthy Female Volunteers

Intramuscular (IM) oxytocin is the gold standard prophylactic therapy for post partum haemorrhage (PPH). However, in resource-poor settings within the developing world, the stability and therefore effectiveness of prophylactic IM oxytocin is diminished by a lack of appropriate refrigeration facilities and availability of trained health care professionals (HCPs) to administer IM injections. This study will be the first investigation of oxytocin in humans via the inhaled (IH) route and is designed to evaluate the safety and tolerability of inhaled oxytocin and the five non-pharmacologically active components in the placebo, and to establish the PK characteristics of up to four fixed escalating doses of inhaled oxytocin. In this single blind ascending dose-escalation study, the systemic exposure from up to four proposed escalating inhaled fixed-dose levels (50 micrograms [mcg], 200 mcg, 400 mcg and 600 mcg) will be compared with the systemic exposure following 10 international units (IU) of IM oxytocin in healthy premenopausal females.. A total of 15 subjects will be enrolled after screening sufficient number of healthy female subjects and the subjects will be assigned to one of the two treatment sequences. The total duration of this study is approximately 20 weeks.

Being tested
IM oxytocin 10 IU, IH oxytocin 50 mcg, IH oxytocin 200 mcg, IH oxytocin 400 mcg, IH oxytocin 600 mcg
Keywords
Pharmacokinetics, safety, tolerability, oxytocin
Medical subject headings
Postpartum Hemorrhage

What participants receive

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

  • IM oxytocin 10 IUDrug

    IM oxytocin 10 IU is a colourless and clear sterile solution in a 1 mL ampoule containing 10 IU of oxytocin, which is administered intramuscularly

  • IH oxytocin 50 mcgDrug

    IH oxytocin 50 mcg is a powder blend for inhalation in a hard capsule containing 50 mcg of oxytocin, which is administered by oral inhalation.

  • IH oxytocin 200 mcgDrug

    IH oxytocin 200 mcg is a powder blend for inhalation in a hard capsule containing 200 mcg of oxytocin, which is administered by oral inhalation.

  • IH oxytocin 400 mcgDrug

    IH oxytocin 400 mcg is a powder blend for inhalation in a hard capsule containing 400 mcg of oxytocin, which is administered by oral inhalation.

  • IH oxytocin 600 mcgDrug

    IH oxytocin 600 mcg is a powder blend for inhalation in a hard capsule containing 600 mcg of oxytocin, which is administered by oral inhalation.

  • PlaceboDrug

    Placebo is a powder blend for inhalation in a hard capsule containing five inactive components, which is administered by oral inhalation.

Study groups in NCT02542813
Study groupRoleWhat they receive
IM oxytocin - IH placebo/IH oxytocin (50, 200, 400, 600)ExperimentalSubjects will receive IM oxytocin, IH placebo/IH oxytocin at doses of 50, 200, 400, 600 mcg.
Receives: Drug: IM oxytocin 10 IU; Drug: IH oxytocin 50 mcg; Drug: IH oxytocin 200 mcg; Drug: IH oxytocin 400 mcg; Drug: IH oxytocin 600 mcg; Drug: Placebo
IM oxytocin - IH placebo/IH oxytocin (50)ExperimentalSubjects will receive IM oxytocin and IH placebo and/or IH oxytocin at 50 mcg.
Receives: Drug: IM oxytocin 10 IU; Drug: IH oxytocin 50 mcg; Drug: Placebo

What is being measured

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

  1. Number of subjects with adverse events (AEs)

    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measured: Up to 16 weeks

  2. Absolute values and changes over time of haematology from pre-dose values as a measure of safety and tolerability

    Hematology assessments will be performed for the following parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, white blood cells (WBC) (absolute), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

    Measured: Up to 20 weeks

  3. Absolute values and changes over time of clinical chemistry from pre-dose values as a measure of safety and tolerability

    Clinical chemistry assessments will be performed for the following parameters: blood urea nitrogen (BUN), creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, total protein, and albumin.

    Measured: Up to 20 weeks

  4. Absolute values and changes over time of urinalysis from pre-dose values as a measure of safety and tolerability

    Dipstick method will be used to measure pH, glucose, protein, blood and ketones.

    Measured: Up to 20 weeks

  5. Absolute values and changes over time of blood pressure from pre-dose values as a measure of safety and tolerability

    Three readings of blood pressure will be taken at screening (single readings at all other time-points).

    Measured: Up to 20 weeks

  6. Absolute values and changes over time of pulse rate from pre-dose values as a measure of safety and tolerability

    Three readings of pulse rate will be taken at screening (single readings at all other time-points).

    Measured: Up to 20 weeks

  7. Absolute values and changes over time of heart rate from pre-dose values as a measure of safety and tolerability

    Absolute values and changes over time of heart rate from pre-dose values as a measure of safety and tolerability.

    Measured: Up to 20 weeks

  8. Absolute values and changes over time of 12-lead electrocardiogram (ECG) parameters (PR, QRS, QT, corrected QT [QTc] intervals) from pre-dose values as a measure of safety and tolerability

    Triplicate 12-lead ECGs will be obtained screening and predose (predose IM oxytocin), and single 12-lead ECGs at all other time-points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.

    Measured: Up to 20 weeks

  9. Number of subjects with adverse respiratory events as monitored by spirometry including forced expiratory volume in 1 second (FEV1.0) and pulse oximetry as a measure of specific respiratory safety

    FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity. Pulse oximetry is a procedure used to measure the oxygen level (or oxygen saturation) in the blood.

    Measured: Up to 16 weeks

  10. Plasma concentration profile for IH oxytocin

    Blood samples will be withdrawn from subjects at pre dose, 3 minutes (mins), 5 mins, 10 mins, 20 mins, 0.5h, 0.75h, 1 hour (h), 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 8 h, and 24 h (24 h post dose assessments only applicable to Dosing Session 1, Group 1 and the first 3 subjects at each new dose level [Dosing Sessions 2 -4]).

    Measured: Day 1, 2, and 3 of dosing session 1, and Day 1 of dosing session 2, 3, and 4

  11. Plasma concentration profile for 10 IU IM oxytocin

    Blood samples will be withdrawn from subjects at pre dose, 3 mins, 5 mins, 10 mins, 20 mins, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, and 8 h.

    Measured: Day 1, 2, and 3 of dosing session 1, and Day 1 of dosing session 2, 3, and 4

  12. Composite PK parameters for IH oxytocin: maximum plasma concentration (Cmax), last quantifiable concentration (Clast), time to Cmax (tmax), area under the plasma concentration-time curve (AUC) and terminal phase half-life (t1/2)

    Blood samples will be withdrawn from subjects at pre dose, 3 mins, 5 mins, 10 mins, 20 mins, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 8 h, and 24 h (24 h post dose assessments only applicable to Dosing Session 1, Group 1 and the first 3 subjects at each new dose level [Dosing Sessions 2 -4]).

    Measured: Day 1, 2, and 3 of dosing session 1, and Day 1 of dosing session 2, 3, and 4

  13. Composite PK parameters for 10 IU IM oxytocin: Cmax, Clast, tmax, AUC and t1/2

    Blood samples will be withdrawn from subjects at pre dose, 3 mins, 5 mins, 10 mins, 20 mins, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, and 8 h.

    Measured: Day 1, 2, and 3 of dosing session 1, and Day 1 of dosing session 2, 3, and 4

Secondary outcomes (1)

  1. Composite of PK parameters: Cmax and AUC will be compared as data permit

    For IM oxytocin: Blood samples will be withdrawn from subjects at pre dose, 3 mins, 5 mins, 10 mins, 20 mins, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, and 8 h.For IH oxytocin: Blood samples will be withdrawn from subjects at pre dose, 3 mins, 5 mins, 10 mins, 20 mins, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 8 h, and 24 h (24 h post dose assessments only applicable to Dosing Session 1, Group 1 and the first 3 subjects at each new dose level [Dosing Sessions 2 -4]).

    Measured: Day 1, 2, and 3 of dosing session 1, and Day 1 of dosing session 2, 3, and 4

Timeline

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

  1. First posted7 Sep 2015 (estimated)
  2. Study start14 Sep 2015
  3. Primary completion16 Dec 2015
  4. Study completion16 Dec 2015

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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02542813
Sponsor's protocol ID
201558
Status last verified
Oct 2017
First submitted
3 Sep 2015
Last updated
19 Oct 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Fernando D, Siederer S, Singh S, Schneider I, Gupta A, Powell M, Richards D, McIntosh MP, Lambert P, Fowles S. Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study. EBioMedicine. 2017 Aug;22:249-255. doi: 10.1016/j.ebiom.2017.07.020. Epub 2017 Jul 22.

    PubMed 28781129

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IM oxytocin 10 IU, IH oxytocin 50 mcg and IH oxytocin 200 mcg in people with Postpartum Hemorrhage, run by GlaxoSmithKline at 1 site in United Kingdom.

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 24 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: finished, as of the sponsor's last update on 19 Oct 2017. 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 United Kingdom. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 subjects with adverse events (AEs) (time frame: Up to 16 weeks). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02542813, which also lists 1 linked publication.

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 19 Oct 2017.

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