Comparison of Inhaled Oxytocin (IH) With Intramuscular (IM) Oxytocin in Pregnant Women and With Intravenous (IV) Oxytocin in Healthy Non-pregnant Women

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-23

Study Completion Date

2019-03-04

Brief Summary

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The study will evaluate a stable, dry-powder formulation of oxytocin, with the goal of reducing post-partum hemorrhage morbidity and mortality in resource poor settings. This study is being conducted to further assess safety and tolerability of inhaled oxytocin, and to characterize the drug levels of inhaled (IH) oxytocin when compared to oxytocin administered as standard of care. Two groups of subjects will be enrolled. Group 1 will enroll pregnant women, who will be randomized to receive either IH or intramuscular (IM) oxytocin as active management of the third stage of labour (after the baby is born). Group 2 will enroll non-pregnant women of childbearing potential, who will receive IH oxytocin and intravenous (IV) oxytocin in a cross over design over two dosing sessions This group will evaluate the safety and tolerability of IH and IV oxytocin.

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Detailed Description

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Conditions

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Postpartum Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

IH Oxytocin

Intervention Type 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).

ROTAHALER

Intervention Type DEVICE

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

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

Group Type EXPERIMENTAL

IM Oxytocin

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

IH Oxytocin

Intervention Type 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).

IV Oxytocin

Intervention Type DRUG

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.

ROTAHALER

Intervention Type DEVICE

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

Interventions

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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).

Intervention Type DRUG

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

Intervention Type DRUG

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.

Intervention Type DRUG

ROTAHALER

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

Intervention Type DEVICE

Eligibility Criteria

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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.

Exclusion Criteria

* 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.

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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes