None listed
Conditions
Brief summary
To evaluate the pharmacokinetics, safety and tolerability of a novel dry powder oxytocin inhaler in comparison to oxytocin intravenous and intramuscular injections. To assess and quantify how effectively oxytocin can be delivered into the human blood stream as a powder from an inhalation device compared with delivery via an intravenous or intramuscular injection. In addition to assess if oxytocin can be delivered as a powder from an inhalation device without causing adverse effects to the recipient
Interventions
All subjects to complete all dosing sessions.
Dosing Session 1 (DS1) (to be completed on 4 consecutive days, all subjects receive all 4 treatments in a randomised order):
Oxytocin dry powder inhaler 150mcg single dose
Oxytocin dry powder inhaler placebo single dose
Oxytocin 10IU intramuscular injection - Comparator - Single dose
Oxytocin 5IU intravenous injection (administered over 5 mins) - Comparator - Single dose
Dosing Session 2 (DS2) (to be completed as soon as possible on completion of DS
All subjects to complete all dosing sessions. Dosing Session 1 (DS1) (to be completed on 4 consecutive days, all subjects receive all 4 treatments in a randomised order): Oxytocin dry powder inhaler 150mcg single dose Oxytocin dry powder inhaler placebo single dose Oxytocin 10IU intramuscular injection - Comparator - Single dose Oxytocin 5IU intravenous injection (administered over 5 mins) - Comparator - Single dose Dosing Session 2 (DS2) (to be completed as soon as possible on completion of DS1 with a minimum of 24hrs between dosing sessions): Each subject to be randomised to receive one of the following: Oxytocin dry powder inhaler 600mcg single dose (14 Subjects) Oxytocin dry powder inhaler placebo single dose (2 Subjects) Dosing Session 3 (DS3) (to be completed 12 weeks after DS2, subjects to be randomised to placebo or active): Oxytocin dry powder inhaler 900mcg single dose (administered as 3x300mcg doses with no interval between doses) - 7 subjects Oxytocin dry powder inhaler placebo single dose (administered as 3x single placebo dose with no interval between doses) - 1 subject Oxytocin dry powder inhaler 300mcg (three doses administered at 10 minute intervals for a total dose of 900mcg) - 7 Subjects Oxytocin dry powder inhaler placebo (three doses administered at 10 minute intervals) - 1 subject. All interventions will be administered under close clinical supervision at the clinical pharmacology unit. Dosing session 1 will be completed with subjects remaining in the unit on an inpatient basis. Placebo dry powder inhaler comprises trehalose, leucine and calcium chloride and is identical to the active dry powder inhaler with the exception that the active component is replaced by trehalose.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Primary purpose
Prevention
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Premenopausal women 18 to 45 years of age, inclusive. 2. Healthy on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and at admission to the study center. 3. Healthy on the basis of clinical laboratory tests performed at screening and at admission to the study center. 4. Must be physically capable of using an oral inhalation dry-powder-inhaler device without physical assistance. 5. Must have FEV1.0 within normal range at screening and before the start of administration of each treatment. 6. Body weight not less than 45 kg and body mass index (BMI; weight kg/m2) within the range of 18 – 30 kg/m2 (inclusive). 7. Premenopausal woman: All women must be of childbearing potential 8. All women must have a negative highly sensitive serum (human chorionic gonadotropin [hCG]) at screening and a negative urine pregnancy test on Day -1 (or on Day 1) of Dosing Session 1 and must not be lactating. 9. All women must be using two methods of contraception, including a combined estrogen-containing OCP for a 30-day minimum period before screening, and must be willing to continue using two methods of contraception, including their current OCP schedule, for the duration of the study and until completion of the follow-up visit. 10. A woman must agree not to donate eggs (ova, oocytes), or freeze for future use, for the purposes of assisted reproduction during the study and for a period of at least 30 days after the last dosing day. 11. Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. Other Inclusions 12. Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic.
Exclusion criteria
1. History of or current clinically significant medical illness 2. Chronic lung condition of any aetiology including adult asthma, chronic obstructive pulmonary disease (COPD), emphysema, bronchospastic respiratory disease and interstitial lung diseases. 3. Underlying cardiovascular diseases (including hypertrophic cardiomyopathy, valvular heart disease, and/or ischemic heart disease including coronary artery vasospasm). 4. Previous or current clinical history of proven pulmonary or systemic tuberculosis. 5. Proven or suspected respiratory tract infection / pneumonia of any aetiology within 4 weeks of screening. 6. History of pulmonary embolus, pulmonary hypertension of any aetiology, and peripheral venous thromboembolism. 7. Use of an intrauterine device (IUD) within last 3 months prior to screening. 8. Any pregnancy within the last 12 months prior to screening. 9. Gynecological disorders or other diseases which can increase the risk of pelvic fibrosis. 10. Alanine transaminase (ALT) [or aspartate transaminase (AST)] >1.5 x upper limit of normal (ULN). 11. Total bilirubin >1.5 x ULN (isolated total bilirubin >1.5 x ULN is allowed for those participants with known Gilbert’s syndrome; Gilbert’s syndrome is suggested by direct bilirubin <30%). 12. Current or chronic history of liver disease. 13. Known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 14. Known allergies, hypersensitivity, or intolerance to IH oxytocin or oxytocin injection, or their excipients. 15. History of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation such as – allergy to latex; allergy to any previous inhaler use. 16. Contraindications to the use of oxytocin injection per local prescribing information 17. Taken any disallowed therapies before the planned first dose of study intervention. 18. Received an investigational intervention, including investigational vaccines, or used an invasive investigational medical device within 1 month or within a period less than 5 times the drug’s half-life, if known, whichever is longer, before the planned first dose of study intervention, or received an investigational biological product within 3 months or 5 half-lives, whichever is longer, before the planned study intervention. In case the half-life of the biological product is not known, the exclusion window will be 6 months before the first dosing day. 19. Is currently enrolled in an investigational study. 20. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. 21. Had major surgery, (eg, requiring general anesthesia) within 3 months before screening (if fully resolved with no further follow up required), or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 60 days after the last dose of study intervention administration. 22. Current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening. 23. Presence of hepatitis B surface antigen (HBsAg) [or hepatitis B core antibody (HBcAb)] at screening or within 3 months prior to first dose of study intervention. 24. Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. 25. History of hepatitis A within 3 months prior to screening or current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]). 26. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator. 27. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 3 years before screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opioids, cocaine, cannabinoids, amphetamines, hallucinogens such as Phencyclidine (PCP), and benzodiazepines) at screening. 28. A positive urine drug test and/or alcohol test may be repeated once (as soon as possible and within the screening period) to exclude a technical error. Participants with a negative urine drug and/or alcohol test at retest may be included. 29. Known allergy to heparin or history of heparin induced thrombocytopenia. 30. Donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study. 31. Must not have used nicotine-containing substances including tobacco products (eg, cigarettes, e-cigarettes, cigars, chewing tobacco, gum, or patch) for at least 1 month prior to screening and not more than one cigarette per week for 3 months prior to screening. 32. Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 8 weeks after the last dose of study intervention. 33. Vulnerable participant (eg, incarcerated individual). 34. Lack of good/reasonable venous access. 35. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Outcome results
None listed