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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02999100




Registration number
NCT02999100
Ethics application status
Date submitted
1/11/2016
Date registered
21/12/2016
Date last updated
23/03/2020

Titles & IDs
Public title
Comparison of Inhaled Oxytocin (IH) With Intramuscular (IM) Oxytocin in Pregnant Women and With Intravenous (IV) Oxytocin in Healthy Non-pregnant Women
Scientific title
A Randomized, Open-label Study to Characterize the Pharmacokinetics of Inhaled Oxytocin (GR121619) Compared With IM Oxytocin in Women in the Third Stage of Labour, and With IV Oxytocin in Non-pregnant, Non-lactating Women of Childbearing Potential
Secondary ID [1] 0 0
2016-002672-27
Secondary ID [2] 0 0
205920
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postpartum Hemorrhage 0 0
Condition category
Condition code
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IH Oxytocin
Treatment: Drugs - IM Oxytocin
Treatment: Drugs - IV Oxytocin
Treatment: Devices - ROTAHALER

Experimental: Group 1 -IH oxytocin - Women with an uncomplicated pregnancy in third stage of labour will be enrolled in the arm. Subjects will receive 400 micrograms (mcg) IH oxytocin. Subjects will be followed up in-person or via telephone within approximately 24 hr post dose and once between 7 days to 14 days

Experimental: Group 1 -IM oxytocin - Women with an uncomplicated pregnancy in third stage of labour will be enrolled in the arm. Subjects will receive 10 I.U. IM oxytocin. Subjects will be followed up in-person or via telephone within approximately 24 hr post dose and once between 7 days to 14 days

Experimental: Group 2 (IH and IV oxytocin) - Group 2 will enrol healthy, non-pregnant, non-lactating female subjects of childbearing potential, and each subject will participate in 2 dosing sessions. Group 2 will be divided into two cohorts: Cohort A will enrol women on a combined oral contraceptive, and Cohort B will enrol women who are not using a hormonal form of contraceptive. Group 2 subjects will randomized to receive IH oxytocin, and IV oxytocin in a cross fashion. Subjects will be followed up in-person once between 7 days to 21 days


Treatment: Drugs: IH Oxytocin
Oxytocin will be supplied as colourless and clear hard capsule with powder blend for inhalation with unit dose strength 400 mcg and 200 mcg. It will be administered using ROTAHALER dry powder inhaler (DPI).

Treatment: Drugs: IM Oxytocin
Oxytocin will be supplied for solution for infusion in 1ml ampoule containing colourless and clear sterile solution with unit dose strength 5 I.U./mL, or 10 I.U./mL for IM administration

Treatment: Drugs: IV Oxytocin
Oxytocin will be supplied as solution for infusion in 1ml ampoule containing colourless and clear sterile solution to be administered as a 30-second IV bolus with unit dose strength 5 I.U./mL, or 10 I.U./mL.

Treatment: Devices: ROTAHALER
ROTAHALER DPI device is a high airflow resistance capsule-based inhaler. It will be used to deliver IH oxytocin

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Plasma Concentration Time Profile of Oxytocin
Timepoint [1] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours, 3 hours and 4 hours post dose Day 1
Primary outcome [2] 0 0
Part 1: Maximum Observed Plasma Concentration (Cmax) of Oxytocin
Timepoint [2] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours, 3 hours and 4 hours post dose Day 1
Primary outcome [3] 0 0
Part 1: Observed Plasma Concentration (Cp) 10 of Oxytocin
Timepoint [3] 0 0
10 minutes post dose Day 1
Primary outcome [4] 0 0
Part 1: Observed Plasma Concentration (Cp) 20 of Oxytocin
Timepoint [4] 0 0
20 minutes post dose Day 1
Primary outcome [5] 0 0
Part 1: Observed Plasma Concentration (Cp) 30 of Oxytocin
Timepoint [5] 0 0
30 minutes post dose Day 1
Primary outcome [6] 0 0
Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Oxytocin
Timepoint [6] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours, 3 hours and 4 hours post dose Day 1
Primary outcome [7] 0 0
Part 1: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Oxytocin
Timepoint [7] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours, 3 hours and 4 hours post dose on Day 1
Primary outcome [8] 0 0
Part 1: Terminal Phase Half-life (t1/2) of Oxytocin
Timepoint [8] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours, 3 hours and 4 hours post dose on Day 1
Primary outcome [9] 0 0
Part 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Up to 37 days
Primary outcome [10] 0 0
Part 2: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [10] 0 0
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose
Primary outcome [11] 0 0
Part 2: Change From Baseline in SBP and DBP
Timepoint [11] 0 0
Baseline (Day 1, pre-dose), 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose
Primary outcome [12] 0 0
Part 2: Change From Baseline in Heart Rate
Timepoint [12] 0 0
Baseline (Day 1, pre-dose), 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose
Primary outcome [13] 0 0
Part 2: Absolute Values of Heart Rate
Timepoint [13] 0 0
Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose
Primary outcome [14] 0 0
Part 2: Absolute Values of PR Interval, QRS Duration, Corrected QT Interval Using Bazett's (QTcB) Formula and Corrected QT Interval Using Fredericia's Formula (QTcF) Interval
Timepoint [14] 0 0
Pre-dose, 2 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour and 4 hours post dose
Primary outcome [15] 0 0
Part 2: Number of Participants With Abnormal Respiratory Events
Timepoint [15] 0 0
Up to Day 37
Primary outcome [16] 0 0
Part 2: Forced Expiratory Volume at 1 Minute (FEV1)
Timepoint [16] 0 0
Pre dose and 1 hour post dose on Day1
Primary outcome [17] 0 0
Part 2: Percent Oxygen in Blood
Timepoint [17] 0 0
Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post-dose
Primary outcome [18] 0 0
Part 2: Absolute Values of Respiration Rate
Timepoint [18] 0 0
Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post-dose
Primary outcome [19] 0 0
Part 2: Plasma Concentration Time Profile of Oxytocin.
Timepoint [19] 0 0
-1 hour,-30 minutes,-15 minutes pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [20] 0 0
Part 2: Maximum Observed Plasma Concentration (Cmax) of Oxytocin
Timepoint [20] 0 0
-1 hour,-30 minutes,-15 minutes pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [21] 0 0
Part 2: Observed Plasma Concentration (Cp)10 of Oxytocin
Timepoint [21] 0 0
10 minutes post dose
Primary outcome [22] 0 0
Part 2: Observed Plasma Concentration (Cp)20 of Oxytocin
Timepoint [22] 0 0
20 minutes post dose
Primary outcome [23] 0 0
Part 2: Observed Plasma Concentration (Cp)30 of Oxytocin
Timepoint [23] 0 0
30 minutes post dose
Primary outcome [24] 0 0
Part 2: Time to Reach Maximum Observed Concentration (Tmax) of Oxytocin
Timepoint [24] 0 0
-1 hour,-30 minutes,-15 minutes pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [25] 0 0
Part 2: Area Under the Concentration-time Curve From Time Zero Extrapolated to Time 't' (AUC[0-t]) of Oxytocin
Timepoint [25] 0 0
-1 hour,-30 minutes,-15 minutes Pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [26] 0 0
Part 2: Plasma Clearance (CL) of Oxytocin for IV Route Only
Timepoint [26] 0 0
-1 hour,-30 minutes,-15 minutes Pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [27] 0 0
Part 2: Volume of Distribution (VOD) of Oxytocin for IV Route Only
Timepoint [27] 0 0
-1 hour,-30 minutes,-15 minutes Pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Primary outcome [28] 0 0
Part 2: Time to Reach Terminal Phase Half-life (t1/2) of Oxytocin
Timepoint [28] 0 0
-1 hour,-30 minutes,-15 minutes pre-dose, 2 minutes, 3 minutes, 5 minutes, 8 minutes,10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours and 4 hours post dose
Secondary outcome [1] 0 0
Part 1: Number of Participants With Non-SAEs and SAEs
Timepoint [1] 0 0
Up to 15 days
Secondary outcome [2] 0 0
Part 1: Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [2] 0 0
30 minutes and 2 hours post dose
Secondary outcome [3] 0 0
Part 1: Absolute Values of Heart Rate
Timepoint [3] 0 0
30 minutes and 2 hours post dose
Secondary outcome [4] 0 0
Part 1: Absolute Values of Respiration Rate
Timepoint [4] 0 0
30 minutes and 2 hours post dose
Secondary outcome [5] 0 0
Part 1: Absolute Values of Temperature
Timepoint [5] 0 0
30 minutes and 2 hours post dose
Secondary outcome [6] 0 0
Part 1: Change From Baseline in SBP and DBP
Timepoint [6] 0 0
Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose
Secondary outcome [7] 0 0
Part 1: Change From Baseline in Heart Rate
Timepoint [7] 0 0
Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose
Secondary outcome [8] 0 0
Part 1: Change From Baseline in Respiration Rate
Timepoint [8] 0 0
Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose
Secondary outcome [9] 0 0
Part 1: Change From Baseline in Body Temperature
Timepoint [9] 0 0
Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose
Secondary outcome [10] 0 0
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Three Hours (AUC ([0-3]) of Oxytocin
Timepoint [10] 0 0
Predose, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 2.5 hours and 3 hours post dose on Day 1

Eligibility
Key inclusion criteria
All Groups:

* Between 18 and 40 years of age inclusive, at the time of signing the informed consent.
* Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, and laboratory tests as required per protocol.
* Subject clinical chemistry and haematology values within an acceptable range for the population recruited and not of abnormal clinical significance. 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.
* Adequate peripheral venous access for cannulation.

Group 1 Only:

* Currently pregnant, with an uncomplicated pregnancy as determined by the investigator or designee.
* Estimated date of delivery within 24 weeks of screening.
* Planned spontaneous vaginal birth and considered by investigator at low risk for post partum hemorrhage (PPH).
* Planned birth in between the 37th and 42nd week of pregnancy.
* Women who qualify for oxytocin as appropriate for active management of TSL and who agree to have active management.

Group 2 Only:

* ECG normal, or abnormal and not clinically significant.
* FEV1 >80% of predicted.
* Systolic blood pressure >=90 millimeters of mercury (mmHg).
* Body mass index (BMI) within the range 18 - 32 Kilogram (kg)/square meter (m^2) (inclusive).
* Sex-Female.
* Group 2, Cohort A Only:

A female subject is eligible to participate if she is confirmed to be not pregnant at screening and on Day 1 (as confirmed by a negative serum or urine human chorionic gonadotrophin [hCG] test), not lactating, and the following condition applies:

Is of reproductive potential and agrees to use the same combined estrogen and progestogen oral contraceptive from 3 months prior to the first dose of study medication and until the follow-up contact.

This method of contraception is only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use their method of contraception

* Group 2, Cohort B Only:

A female subject is eligible to participate if she is confirmed to be not pregnant at screening and on Day 1 (as confirmed by a negative serum or urine hCG test), not lactating, and one of the following conditions applies:

Is of reproductive potential and has been using the same non-hormonal contraceptive method from 3 months prior to the first dose of study medication and until the follow-up contact.

Would be of reproductive potential, but has undergone bilateral tubal ligation or occlusion or bilateral salpingectomy at least 12 months prior to first dose of study medication.

Is of reproductive potential with only same sex partners or who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis, when this is their preferred and usual lifestyle. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

These methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use their method(s) of contraception.

Of Note: Group 2, Cohort B will enrol women of reproductive potential if they agree to use a nonhormonal contraceptive method from at least one month prior to receiving study drug and until the follow-up assessment. Although condoms with spermicide are not considered a highly effective method of contraception, the risk of receiving study drug during pregnancy is minimal for the following reasons:

Pregnancy testing must be negative at screening and on the first day of dosing. Dosing is completed no greater than 14 days from the start of dosing. Oxytocin has a well established rapid half-life. If a patient happened to conceive during the time of dosing, study drug would be eliminated before implantation would occur.

* All Groups: 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.
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All Groups:

* Postmenopausal as defined by gynaecological history.
* Chronic lung condition of any etiology including asthma, Chronic obstructive pulmonary disease (COPD), emphysema, interstitial lung disease or active Tuberculosis (TB).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Blood pressure >140 systolic or >90 diastolic.

Group 1 Only:

* Females with planned Caesarean Section.
* Females with significant medical complications as determined by investigator.

Group 2 Only:

* Currently breastfeeding or lactating.
* QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds (msec).
* Alanine aminotransferase (ALT) and bilirubin >1.5 Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
* Subjects with highly-active or symptomatic gynaecological disorders (such as large symptomatic fibroids).

All Groups:

* Prescription or non-prescription drugs not approved by the investigator.
* Oxytocin for any reason (including, but not limited to, induction or augmentation of labour) prior to administration of study-related oxytocin.
* History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 units. 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.
* Current smokers or subjects with a history of smoking within 6 months of screening, or with a total pack year history of >5 pack years. 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 (e.g. allergy to any previous inhaler use).
* Participation in another clinical trial, which in the opinion of the investigator, jeopardizes the subject's safety or study outcomes.
* 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 investigation product within the following time period prior to the first dosing day in the current study: 30 days 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.

Group 2 Only:

* Presence of hepatitis B surface antigen or positive hepatitis C antibody test result.
* A positive Human Immunodeficiency Virus (HIV) antibody test.
* A positive pre-study drugs of abuse test (not explained by diet or approved concomitant medications).
* A positive alcohol breath test.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Cambridgeshire
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Cambridge

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
InVentiv Clinique
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Monash University
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.