Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03464864
• Date of registration: 01/03/2018
• Prospective Registration: Yes
• Primary sponsor: Mannkind Corporation
• Public title: Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers
• Scientific title: A Phase 1, Single-center, Open-label, Dose-Rising Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder (TrIP) in Healthy Normal Volunteers
• Date of first enrolment: March 9, 2018
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03464864
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Senior Director, Clinical Pharmacology
• Affiliation: Mannkind Corporation

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Voluntarily consents to participate in this study and provides written informed
consent prior to the start of any study-specific procedures.

2. Male or female. Females must not be pregnant or breastfeeding.

3. Is between 18 and 55 years of age (inclusive).

4. Female subjects must weigh between 55 and 100 kg, inclusive, with a body mass index
(BMI) between 19.0-32.0 kg/m2, inclusive. Male subjects must weigh between 55 and 120
kg, inclusive, with a BMI between 19.0-32.0 kg/m2, inclusive.

5. Females must be of non-childbearing potential (defined as surgically sterile [i.e. had
a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months
prior to the first dose of study medication] or postmenopausal for at least 1 year
prior to the first dose of study medication) or agree to use an acceptable form of
birth control (see Section 4.4) from screening until 14 days after study completion.

6. Medical history, physical examination, oropharyngeal examination, vital signs, ECG,
spirometry, and clinical laboratory results within normal limits or considered not
clinically significant by the Investigator at screening.

Exclusion Criteria:

1. History or presence of clinically significant cardiovascular, pulmonary, hepatic,
renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,
neurologic, oncologic, or psychiatric disease or any other condition that, in the
opinion of the Investigator, would jeopardize the safety of the subject or the
validity of the study results.

2. A clinically significant abnormal finding on the physical exam, medical history,
electrocardiogram (ECG), or clinical laboratory results at screening.

3. History of chronic lung disease such as asthma, chronic obstructive pulmonary disease
(COPD), cystic fibrosis, interstitial lung disease, pulmonary fibrosis, etc.

4. History of migraine headaches.

5. History of a bleeding abnormalities (i.e., gingival bleeding, epistaxis, or blood on
toilet paper, etc.) that is judged to be significant by the Investigator.

6. Has forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio <
80% predicted or FEV25-75 <50% predicted.

7. History of anaphylaxis, a documented hypersensitivity reaction, or a clinically
significant idiosyncratic reaction to any drug.

8. Has been on a significantly abnormal diet (as determined by the Investigator) during
the 4 weeks preceding the first dose of study medication.

9. Has participated in another clinical trial (and received an investigational product)
within 30 days prior to the first dose of study medication.

10. Use of any over-the-counter (OTC) medication (including nutritional or dietary
supplements, herbal preparations, or vitamins) within 7 days prior to the first dose
of study medication until the end of study visit without evaluation and approval by
the Medical Monitor.

11. Use of any prescription medication, except hormonal contraceptive or hormonal
replacement therapy, from 14 days prior to the first dose of study medication until
the end-of-study visit without evaluation and approval by the Investigator.

12. Has been treated with any known drugs that are moderate or strong inhibitors/inducers
of cytochrome P450 (CYP) enzymes (e.g., barbiturates, phenothiazines, cimetidine,
carbamazepine) within 30 days prior to the first dose of study medication, and that,
in the Investigator's judgment, may impact subject safety or the validity of the study
results.

13. Blood or plasma donation within 30 days prior to the first dose of study medication.

14. Smoking or use of tobacco- or nicotine-containing products within 6 months prior to
the first dose of study medication until the end-of-study visit.

15. Engagement in strenuous exercise within 48 hours prior to the first dose of study
medication.

16. Consumption of beverages or foods that contain alcohol, grapefruit, poppy seeds,
broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or
caffeine/xanthine from 48 hours prior to the first dose of study medication until the
end-of-study visit. Subjects will be instructed not to consume any of the above
products; however, allowance for an isolated single incidental consumption may be
evaluated and approved by the study Investigator based on the potential for
interaction with the study drug.

17. Has any prior history of substance abuse or treatment (including alcohol).

18. Is a female with a positive pregnancy test result or who is breastfeeding.

19. Has a positive urine screen for drugs of abuse (amphetamines, barbiturates,
benzodiazepines, cocaine, cannabinoids, opiates) or cotinine.

20. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human
immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis
B, hepatitis C, or HIV infection.

21. Unwilling to remove any artificial nails (e.g. acrylic, gel) or fingernail polish and
to not use such products for the duration of the study.

22. Inability to perform study procedures including pulmonary function testing.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Treprostinil Inhalation Powder

Primary Outcome(s)

Incidence and severity of treatment-related adverse events (safety and tolerability) of single ascending doses of Treprostinil Inhalation Powder [Time Frame: At protocol-specified time points from the time of screening (day 0) to end of study (day 6)]

Secondary Outcome(s)

Dose proportionality [Time Frame: 10 months]

Systemic exposure and pharmacokinetics of treprostinil administered as Treprostinil Inhalation Powder in healthy normal volunteers [Time Frame: At protocol-specified time points throughout day 1]

Secondary ID(s)

MKC-475-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors