Comparison of Inhaled Oxytocin (IH) With Intramuscular (I... | NCT02999100

ID	Type	Description	Link
2016-002672-27	EudraCT Number

Name	Class
InVentiv Clinique	INDUSTRY
Monash University	OTHER

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1 -IH oxytocin	Experimental	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	Drug: IH Oxytocin Device: ROTAHALER
Group 1 -IM oxytocin	Experimental	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	Drug: IM Oxytocin
Group 2 (IH and IV oxytocin)	Experimental	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	Drug: IH Oxytocin Drug: IV Oxytocin Device: ROTAHALER

Interventions

Name	Type	Description	Arm Group Labels	Other Names
IH Oxytocin	Drug	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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Plasma Concentration Time Profile of Oxytocin	Blood samples were collected at indicated time points to evaluate concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.	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
Part 1: Maximum Observed Plasma Concentration (Cmax) of Oxytocin	Blood samples were collected at indicated time points to evaluate Cmax of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.	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
Part 1: Observed Plasma Concentration (Cp) 10 of Oxytocin	Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.	10 minutes post dose Day 1
Part 1: Observed Plasma Concentration (Cp) 20 of Oxytocin	Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.	20 minutes post dose Day 1
Part 1: Observed Plasma Concentration (Cp) 30 of Oxytocin	Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.	30 minutes post dose Day 1

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Number of Participants With Non-SAEs and SAEs	An adverse event is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.

Eligibility Module

Eligibility Criteria

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.

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Clayton	Victoria	3168	Australia
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
37522415	Derived	Oliver VL, Siederer S, Cahn A, Gajewska-Knapik K, Gibson RA, Goodall C, Kirkpatrick C, Murray J, Nguyen TH, Schneider I, Lambert P, McIntosh MP, Parry S. Exploring the role of ex vivo metabolism on blood and plasma measurements of oxytocin among women in the third stage of labour: A post hoc study. Br J Clin Pharmacol. 2023 Dec;89(12):3669-3680. doi: 10.1111/bcp.15865. Epub 2023 Aug 24.
37485589

ID	Title	Description
FG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labor (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 30, 2018	Jan 31, 2020

Arm/Group Information

ID	Title	Description
BG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labor (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
BG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
BG002	Contraceptives+400 mcg Oxytocin IH, Then 8.5mcg Oxytocin IV	Healthy participants of childbearing potential were administered oral contraceptive along with 400 mcg oxytocin IH during Session 1 and received 8.5 mcg oxytocin IV during Session 2. Participants were followed up in-person or via telephone within 7 days and no greater than 21 days after last study drug administration.
BG003	Contraceptives+8.5mcg Oxytocin IV, Then 400 mcg Oxytocin IH	Healthy participants of childbearing potential were administered oral contraceptives along with 8.5 mcg oxytocin IV during Session 1 and received 400 mcg oxytocin IH during Session 2. Participants were followed up in-person or via telephone within 7 days and no greater than 21 days after last study drug administration.
BG004	400 mcg Oxytocin IH, Then 8.5 mcg Oxytocin IV	Healthy participants of childbearing potential were administered 400 mcg oxytocin IH during Session 1 and received 8.5 mcg oxytocin IV during Session 2. Participants were followed up in-person or via telephone within 7 days and no greater than 21 days after last study drug administration.
BG005	8.5 mcg Oxytocin IV, Then 400 mcg Oxytocin IH	Healthy participants of childbearing potential were administered 8.5 mcg oxytocin IV during Session 1 and received 400 mcg oxytocin IH during Session 2. Participants were followed up in-person or via telephone within 7 days and no greater than 21 days after last study drug administration.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Plasma Concentration Time Profile of Oxytocin

Blood samples were collected at indicated time points to evaluate concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population includes all participants in Safety population for whom a pharmacokinetic sample was obtained & analysed.Safety Population includes participants who received at least one dose of study medication.Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles)

Posted

Median

Full Range

Picograms per milliliter

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants	OG0009 OG0018

Title

Denominators

Categories

Pre-dose; n=9, 8

- ParticipantsOG0009
- ParticipantsOG0018

Title	Measurements
	OG0000.000(0.00 to 5.32)

Primary

Part 1: Maximum Observed Plasma Concentration (Cmax) of Oxytocin

Blood samples were collected at indicated time points to evaluate Cmax of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Median

Full Range

Picograms per milliliter

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts

Primary

Part 1: Observed Plasma Concentration (Cp) 10 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Median

Full Range

Picogram per milliliter

10 minutes post dose Day 1

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Primary

Part 1: Observed Plasma Concentration (Cp) 20 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Median

Full Range

Picogram per milliliter

20 minutes post dose Day 1

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Primary

Part 1: Observed Plasma Concentration (Cp) 30 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Median

Full Range

Picogram per milliliter

30 minutes post dose Day 1

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Primary

Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Oxytocin

Blood samples were collected at indicated time points to evaluate Tmax of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed.

Posted

Median

Full Range

Hours

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Primary

Part 1: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Oxytocin

Blood samples were collected at indicated time points to evaluate AUC (0-t) of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Median

Full Range

Hour*picogram per milliliter

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Primary

Part 1: Terminal Phase Half-life (t1/2) of Oxytocin

Blood samples were collected at indicated time points to evaluate t1/2 of oxytocin.

Pharmacokinetic Population.

Posted

Median

Full Range

Hours

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Primary

Part 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. As SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety Population includes participants who received at least one dose of study medication.

Safety Population. Participants analysed (25) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Count of Participants

Participants

Up to 37 days

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.

Primary

Part 2: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Posted

Mean

Standard Deviation

Millimeters of mercury

Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Change From Baseline in SBP and DBP

SBP and DBP of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment with a non-missing value at Day 1 (Pre-dose). Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1, pre-dose), 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion

Primary

Part 2: Change From Baseline in Heart Rate

Heart rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment with a non-missing value at Day 1 (Pre-dose). Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1, pre-dose), 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion

Primary

Part 2: Absolute Values of Heart Rate

Heart rate was measured in semi-supine position after 5 minutes rest

Posted

Mean

Standard Deviation

Beats per minute

Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

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

Triplicate 12-lead electrocardiograms (ECGs) were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measured PR interval, QRS duration, QTcB interval, and QTcF interval.

Posted

Mean

Standard Deviation

Milliseconds

Pre-dose, 2 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour and 4 hours post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002

Primary

Part 2: Number of Participants With Abnormal Respiratory Events

Number of participants with abnormal respiratory events has been presented

Posted

Count of Participants

Participants

Up to Day 37

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.
OG003

Primary

Part 2: Forced Expiratory Volume at 1 Minute (FEV1)

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were taken electronically by spirometry on Day 1. At each time point, three best measurements were recorded.

Posted

Mean

Standard Deviation

Liters

Pre dose and 1 hour post dose on Day1

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Percent Oxygen in Blood

Percent oxygen in blood was measured using pulse oximetry in a semi-supine position after 5 minutes rest. Pulse oximeter is a device that measures oxygen saturation of arterial blood in participants by utilizing a sensor attached typically to a finger, toe, or ear to determine the percentage of oxyhemoglobin in blood pulsating through a network of capillaries

Posted

Mean

Standard Deviation

Percentage of oxygen

Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post-dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion

Primary

Part 2: Absolute Values of Respiration Rate

Respiration rate was measured in semi-supine position after 5 minutes rest

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles). Participants analysed (25) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Mean

Standard Deviation

Breaths per minute

Pre dose, 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours post-dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Plasma Concentration Time Profile of Oxytocin.

Blood samples were collected at indicated time points to evaluate concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles). Participants analysed (25) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Median

Full Range

Picograms per milliliter

-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

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002

Primary

Part 2: Maximum Observed Plasma Concentration (Cmax) of Oxytocin

Blood samples were collected at indicated time points to evaluate Cmax of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. Participants analysed (23) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Geometric Mean

Geometric Coefficient of Variation

Picogram per milliliter

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002

Primary

Part 2: Observed Plasma Concentration (Cp)10 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Participants analysed (25) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Geometric Mean

Geometric Coefficient of Variation

Picogram per milliliter

10 minutes post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Observed Plasma Concentration (Cp)20 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Picogram per milliliter

20 minutes post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Observed Plasma Concentration (Cp)30 of Oxytocin

Blood samples were collected at indicated time points to evaluate observed plasma concentration of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Picogram per milliliter

30 minutes post dose

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.

Primary

Part 2: Time to Reach Maximum Observed Concentration (Tmax) of Oxytocin

Blood samples were collected at indicated time points to evaluate Tmax of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Posted

Median

Full Range

Hours

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion

Primary

Part 2: Area Under the Concentration-time Curve From Time Zero Extrapolated to Time 't' (AUC[0-t]) of Oxytocin

Blood samples were collected at indicated time points to evaluate AUC (0-t) of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*picogram per milliliter

-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

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.

Primary

Part 2: Plasma Clearance (CL) of Oxytocin for IV Route Only

Blood samples were collected at indicated time points to evaluate plasma clearance of oxytocin IV bolus and infusion. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. Only IV reporting arms presented.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

ID	Title	Description
OG000	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.
OG002	Non-Combined Oral Contraceptive+ 8.5 mcg Oxytocin IV Bolus

Primary

Part 2: Volume of Distribution (VOD) of Oxytocin for IV Route Only

Blood samples were collected at indicated time points to evaluate volume of distribution of oxytocin IV bolus and infusion. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. Only IV reporting arms presented.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters

ID	Title	Description
OG000	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.
OG002	Non-Combined Oral Contraceptive+ 8.5 mcg Oxytocin IV Bolus

Primary

Part 2: Time to Reach Terminal Phase Half-life (t1/2) of Oxytocin

Blood samples were collected at indicated time points to evaluate t1/2 of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. Participants analysed (22) is greater than the number participants (14) started in Part 2 because Part 2 is a crossover design and participants were considered for 2 dosing sessions.

Posted

Median

Full Range

Hours

ID	Title	Description
OG000	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH.
OG001	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.
OG002	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion

Secondary

Part 1: Number of Participants With Non-SAEs and SAEs

An adverse event is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.

Safety Population includes participants who received at least one dose of study medication

Posted

Count of Participants

Participants

Up to 15 days

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Secondary

Part 1: Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Millimeters of mercury

30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts

Secondary

Part 1: Absolute Values of Heart Rate

Heart rate was measured in semi-supine position after 5 minutes rest

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Beats per minute

30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Secondary

Part 1: Absolute Values of Respiration Rate

Respiration rate was measured in semi-supine position after 5 minutes rest

Safety Population. Only those participants with data available at specified data points were analyzed.

Posted

Mean

Standard Deviation

Breaths per minute

30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Secondary

Part 1: Absolute Values of Temperature

Body temperature was measured in semi-supine position after 5 minutes rest

Safety Population. Only those participants with data available at specified data points were analyzed.

Posted

Mean

Standard Deviation

Degrees Celsius

30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in SBP and DBP

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Secondary

Part 1: Change From Baseline in Heart Rate

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Secondary

Part 1: Change From Baseline in Respiration Rate

Respiration rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment with a non-missing value at Day 1 (Pre-dose). Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Safety Population. Only those participants with data available at specified data points were analyzed.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Secondary

Part 1: Change From Baseline in Body Temperature

Body temperature was measured at indicated time points in semi-supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment with a non-missing value at Day 1 (Pre-dose). Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Safety Population. Only those participants with data available at specified data points were analyzed.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 1, pre-dose), 30 minutes and 2 hours post dose

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Secondary

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Three Hours (AUC ([0-3]) of Oxytocin

Blood samples were collected at indicated time points to evaluate AUC (0-3) of oxytocin. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Pharmacokinetic Population.

Posted

Mean

Standard Deviation

Hour*picogram per milliliter

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

ID	Title	Description
OG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labo (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.
OG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.

Units

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	400 mcg Oxytocin IH	Participants with uncomplicated pregnancy received 400 micrograms (mcg) IH oxytocin during third stage of labor (within 5 minutes of birth) via ROTAHALER dry powder inhaler (DPI). Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.	9	2	9	3	9
EG001	17 mcg Oxytocin IM	Participants with uncomplicated pregnancy received 17 mcg IM oxytocin injection during third stage of labor (within 5 minutes of birth) in the anterior shoulder. Participants were followed up in-person or via telephone within approximately 24 hours post dose and once between 7 days to 14 days.	8	2	8	2	8
EG002	Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential receiving oral contraceptive along with 400 mcg oxytocin IH	7	0	7	7	7
EG003	Combined Oral Contraceptive+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.	5	0	5	5	5
EG004	Combined Oral Contraceptives+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential receiving oral contraceptive along with 8.5 mcg oxytocin IV.	2	0	2	1	2
EG005	Non-Combined Oral Contraceptives+400 mcg Oxytocin IH	Healthy participants of childbearing potential using a non-hormonal form of contraception along with 400 mcg oxytocin IH.	5	0	5	3	5
EG006	Non-Combined Oral Contraceptive+ 8.5 mcg Oxytocin IV Bolus	Healthy participants of childbearing potential using a non-hormonal form of contraception along with 8.5 mcg oxytocin IV bolus. When the duration of IV oxytocin administered was less than or equal to 2 minutes then the IV dose administered was classified as an IV Bolus.	1	0	1	1	1
EG007	Non-Combined Oral Contraceptive+ 8.5 mcg Oxytocin IV Infusion	Healthy participants of childbearing potential using a non-hormonal form of contraception along with 8.5 mcg oxytocin IV.	5	0	5	5	5

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected9 at risk EG0011 events1 affected8 at risk EG0020 events0 affected7 at risk EG0030 events0 affected5 at risk EG0040 events0 affected2 at risk EG0050 events0 affected5 at risk EG0060 events0 affected1 at risk EG0070 events0 affected5 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0025 events4 affected7 at risk EG003
Flushing	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Hot flush	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0022 events2 affected7 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Feeling hot	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0021 events1 affected7 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0023 events2 affected7 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0022 events2 affected7 at risk EG003
Palpitations	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected8 at risk EG0020 events0 affected7 at risk EG003
Nipple infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Perineal injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected8 at risk EG0020 events0 affected7 at risk EG003
Postpartum haemorrhage	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected8 at risk EG0020 events0 affected7 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected8 at risk EG0020 events0 affected7 at risk EG003

ID	Term
D007744	Obstetric Labor Complications
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D011644	Puerperal Disorders
D014592	Uterine Hemorrhage
D006470	Hemorrhage
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D010909	Pituitary Hormones, Posterior
D010907	Pituitary Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins