Pulmonary Arterial HypertensionPhase 1NCT03464864
Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers
A Phase 1 study testing Treprostinil Inhalation Powder in people with Pulmonary Arterial Hypertension, run by Mannkind Corporation at 1 site in United States.
Trial summary
A Dose-Rising Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Treprostinil Inhalation Powder
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2018to 5 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study-specific procedures.
- Male or female. Females must not be pregnant or breastfeeding.
- Is between 18 and 55 years of age (inclusive).
- 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.
- 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.
- 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.
Who cannot join
- 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.
- A clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
- History of chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung disease, pulmonary fibrosis, etc.
- History of migraine headaches.
- 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.
- Has forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio < 80% predicted or FEV25-75 <50% predicted.
Show all 22Show fewer
- History of anaphylaxis, a documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to any drug.
- Has been on a significantly abnormal diet (as determined by the Investigator) during the 4 weeks preceding the first dose of study medication.
- Has participated in another clinical trial (and received an investigational product) within 30 days prior to the first dose of study medication.
- 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.
- 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.
- 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.
- Blood or plasma donation within 30 days prior to the first dose of study medication.
- 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.
- Engagement in strenuous exercise within 48 hours prior to the first dose of study medication.
- 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.
- Has any prior history of substance abuse or treatment (including alcohol).
- Is a female with a positive pregnancy test result or who is breastfeeding.
- Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) or cotinine.
- 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.
- 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.
- Inability to perform study procedures including pulmonary function testing.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
A Dose-Rising Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers
Read the detailed description
Up to 48 subjects will be enrolled in 8 cohorts of 6 subjects each. The treatments are intended to establish the maximum tolerated dose in healthy normal volunteers, starting at 30 mcg. Each subject will receive one dose of Treprostinil Inhalation Powder by oral inhalation during the treatment period.
A total of 12 pharmacokinetic blood samples will be collected from each subject. Plasma pharmacokinetic samples will be analyzed for treprostinil.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Treprostinil Inhalation Powder
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treprostinil Inhalation PowderDrug
Single ascending dose
| Study group | Role | What they receive |
|---|---|---|
| Treprostinil Inhalation Powder 30 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 60 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 90 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 120 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 150 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 180 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 240 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 300 mcg | Experimental | Not described Receives: Drug: Treprostinil Inhalation Powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-related adverse events (safety and tolerability) of single ascending doses of Treprostinil Inhalation Powder
Incidence and severity of treatment-related adverse events determined by changes from screening (baseline) of findings from physical examinations, laboratory evaluations, vital signs measurements, pulmonary testing, and ECG measurements.
Measured: At protocol-specified time points from the time of screening (day 0) to end of study (day 6)
Secondary outcomes (2)
Systemic exposure and pharmacokinetics of treprostinil administered as Treprostinil Inhalation Powder in healthy normal volunteers
Concentration of treprostinil in blood as measured by protocol-specified pharmacokinetic parameters (eg maximum concentration, time to maximum concentration).
Measured: At protocol-specified time points throughout day 1
Dose proportionality
Dose proportionality of increasing doses of Treprostinil Inhalation Powder in healthy normal volunteers as measured by maximum blood concentration of treprostinil.
Measured: 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start9 Mar 2018
- Primary completion5 Jun 2018
- Study completion5 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mannkind Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Director, Clinical Pharmacology, Study director, Mannkind Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464864
- Sponsor's protocol ID
- MKC-475-001
- Status last verified
- Oct 2018
- First submitted
- 1 Mar 2018
- Last updated
- 30 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03464864
- Acronym / sponsor ID
- MKC-475-001
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Mannkind CorporationIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2018 (actual)
- Primary completion
- 5 Jun 2018 (actual)
- Study completion
- 5 Jun 2018 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Dose-Rising Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Treprostinil Inhalation Powder in Healthy Normal Volunteers
Detailed description
Up to 48 subjects will be enrolled in 8 cohorts of 6 subjects each. The treatments are intended to establish the maximum tolerated dose in healthy normal volunteers, starting at 30 mcg. Each subject will receive one dose of Treprostinil Inhalation Powder by oral inhalation during the treatment period.
A total of 12 pharmacokinetic blood samples will be collected from each subject. Plasma pharmacokinetic samples will be analyzed for treprostinil.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Treprostinil Inhalation Powder 30 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 60 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 90 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 120 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 150 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 180 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 240 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
| Treprostinil Inhalation Powder 300 mcg | Experimental | Drug: Treprostinil Inhalation Powder |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study-specific procedures.
- Male or female. Females must not be pregnant or breastfeeding.
- Is between 18 and 55 years of age (inclusive).
- 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.
- 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.
Key exclusion criteria (22 listed)
- 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.
- A clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
- History of chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung disease, pulmonary fibrosis, etc.
- History of migraine headaches.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treprostinil Inhalation PowderSingle ascending dose | Drug | Treprostinil Inhalation Powder 120 mcg, Treprostinil Inhalation Powder 150 mcg, Treprostinil Inhalation Powder 180 mcg, Treprostinil Inhalation Powder 240 mcg, Treprostinil Inhalation Powder 30 mcg, Treprostinil Inhalation Powder 300 mcg, Treprostinil Inhalation Powder 60 mcg, Treprostinil Inhalation Powder 90 mcg |
Primary outcome
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)
Incidence and severity of treatment-related adverse events determined by changes from screening (baseline) of findings from physical examinations, laboratory evaluations, vital signs measurements, pulmonary testing, and ECG measurements.
2 secondary outcomes
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
Dose proportionality
Time frame: 10 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Individual participant dataSharing planned: Undecided
Related trials for Pulmonary Arterial Hypertension
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Director, Clinical Pharmacology study director
Mannkind Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treprostinil Inhalation Powder in people with Pulmonary Arterial Hypertension, run by Mannkind Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2018.