Comparison of Inhaled oxytocin (IH) with intramuscular (IM) oxytocin in pregnant women and with intravenous (IV) oxytocin in healthy non-pregnant women
Trial overview
Group 1: Plasma concentration time profile for IH oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 1 hour (hr), 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Plasma concentration time profile for IM oxytocin.
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Maximum observed plasma concentration (Cmax) for IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Observed plasma concentrations at defined time intervals post-dose (Cp) for IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: post dose at 10 min, 20 min, and 30 min on Day 1
Group 1: Time to Cmax (tmax) for IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Area under concentration-time curve (AUC) for IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 2: Number of subjects with adverse events
Timeframe: Maximum up to 64 days
Group 2: Absolute values of blood pressure
Timeframe: Day 1
Group 2: Absolute values of heart rate
Timeframe: Day 1
Group 2: Change from Baseline over time in blood pressure
Timeframe: Baseline and up to Day 1
Group 2: Change from Baseline over time in heart rate
Timeframe: Baseline and up to Day 1
Group 2: Absolute values of 12-lead electrocardiogram (ECG) parameters
Timeframe: Day 1
Group 2: Change from Baseline over time in 12-lead electrocardiogram (ECG) parameters
Timeframe: Baseline and up to Day 1
Group 2: Number of subjects with adverse respiratory events
Timeframe: Day 1
Group 2: Forced expiratory volume at 1 minute (FEV1.0)
Timeframe: Day 1
Group 2: Respiratory rate
Timeframe: Day 1
Group 2: Pulse oximetry
Timeframe: Day 1
Group 1: Time to Terminal phase half-life (t1/2) for IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Number of subjects with adverse events (AE)
Timeframe: Maximum up to 14 days
Group 1: Absolute values of blood pressure
Timeframe: Baseline (Day -1) and up to Day 1
Group 1: Absolute values of heart rate
Timeframe: Day 1
Group 1: Absolute values of respiratory rateGroup 1: Absolute values of respiratory rate
Timeframe: Day 1
Group 1: Absolute values of temperature
Timeframe: Day 1
Group 1: Change from Baseline over time in blood pressure
Timeframe: Baseline and up to Day 1
Group 1: Change from Baseline over time in heart rate
Timeframe: Baseline and up to Day 1
Group 1: Change from Baseline over time in respiratory rate
Timeframe: Baseline and up to Day 1
Group 1: Change from Baseline over time in temperature
Timeframe: Baseline and up to Day 1
Group 1: Comparison of Cmax between IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 1: Comparison of Cp between IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: post dose at 10 min, 120 min, and 30 min on Day 1
Group 1: Comparison of Area under the concentration-time curve from time zero (pre-dose) to three hours (AUC[0-3h]) between IH oxytocin and IM oxytocin
Timeframe: Blood samples will be collected at the following time points: Predose, and post dose at 3 min, 5 min, 10 min, 15 min, 20 min, 30 min, 1 hr, 2 hr, 2.5 hr, 3 hr, 4 hr on Day 1
Group 2: Plasma concentration time profile for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Group 2: Cmax for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Group 2: Cp for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: post dose at 10 min, 120 min, and 30 min on Day 1.
Group 2: Tmax for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Group 2: AUC for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Group 2: Plasma clearance (CL) for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Group 2: T1/2 for IH oxytocin and IV oxytocin
Timeframe: Blood samples will be collected at the following time points: Pre-dose, and post dose at 2 min, 3 min, 5 min, 8 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, and 4 hr on Day 1
Participation criteria
- All Groups:
- Between 18 and 40 years of age inclusive, at the time of signing the informed consent.
- All Groups:
- Postmenopausal as defined by gynaecological history.
- 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.
- 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.
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.