Pulmonary Arterial HypertensionPhase 1NCT05938946
Safety, Tolerability and Pharmacokinetics of L608 in Healthy Adults
A Phase 1 study testing L608 Inhalation Solution in people with Pulmonary Arterial Hypertension, run by Pharmosa Biopharm Inc. at 1 site in Australia.
Trial summary
This is a Phase I, randomized, double-blinded, placebo-controlled single ascending dose, sequential-group study to evaluate the safety, tolerability, and PK of single ascending doses of L608 inhalation in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- L608 Inhalation Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteAustralia
- Study dates
- 30 Aug 2023to 2 Sep 2024
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women aged between 18 and 65 (inclusive) at the time of Screening visit. Females must not be pregnant or lactating.
- Body Mass Index (BMI) of ≥18.5 and ≤30.0 kg/m2
- Non-smokers or former smokers who have smoked ≤ 100 cigarettes in their lifetime and have not consumed any tobacco or tobacco-containing products for at least 3 months prior to Screening.
- Females must not be pregnant or lactating and must use acceptable, highly effective double contraception from Screening until 3 months after the last dose of the Investigational product.
Who cannot join
- Subjects with contraindications or sensitivity to any components of the study treatment.
- Subjects with medical histories (within 3 months prior to Screening) or ongoing conditions of any clinically significant and/or any other medical conditions which may jeopardize the safety of the subjects and/or effect the results of the study at the Investigator's discretion.
- Subjects with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.
- Subjects who voluntarily participate in this study and sign the informed consent form prior to any study procedures.
- Subjects with histories or active conditions of asthma, sleep apnea, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchiectasis, bronchospasm, and/or reactive airway. Subjects who have had childhood asthma which have resolved as deemed by the PI can be considered.
- Subjects with histories or active conditions of myocardial infarction (MI), cerebrovascular accident (CVA), coronary artery disease (CAD), unstable angina, heart failure, significant cardiac arrhythmias, congenital or acquired valvular heart disease with clinically insignificant symptom, suspected lung congestion, and/or pulmonary arterial hypertension (PAH) causing by venous thromboembolism.
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- Subjects with systolic blood pressure < 90 mmHg or > 160 mmHg and/or diastolic blood pressure < 50 mmHg or > 95 mmHg at Screening or check-in visit.
- Subjects with FEV1 less than 80% predicted, FVC ˂80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit.
- Subjects with histories of drug or alcohol abuse within 1 year prior to subject check-in (Day -1). Regular alcohol consumption defined as > 10 standard drinks per week.
- Consumption of products containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing and products containing grapefruit and/or pomelo (shown to inhibit cytochrome P450 [CYP] 3A4 activity) within 10 days prior to drug administration.
- Positive results of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and pregnancy test.
- Blood donation or significant blood loss (>480 ml) within 3 months prior to Screening.
- Subjects are pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
Australia1 site
CMAX Clinical Research Pty Ltd
Adelaide, South Australia, SA 5000
About this study
Official title: A Phase I, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of L608 for Inhalation in Healthy Subjects
This is a Phase I, randomized, double-blinded, placebo-controlled single ascending dose, sequential-group study to evaluate the safety, tolerability, and PK of single ascending doses of L608 inhalation in healthy volunteers.
Read the detailed description
L608 inhalation Solution (L608) is developed by Pharmosa Biopharm Inc. (PBI) as a new liposomal Iloprost formulation for inhalation use in the treatment of patients with PAH (WHO Group 1). As a liposomal formulation of iloprost, L608 is intended to reduce the dosing frequency, as well as provide sustained and selective release along with achieving therapeutically relevant iloprost level. Meanwhile, L608 is expected to mitigate burst release related local irritation and systemic side effects (e.g., hypotension due to plasma peak) in clinical practice.
This Phase I, randomized, double-blinded, placebo-controlled study will be conducted in healthy volunteers in Australia to evaluate the safety, tolerability, and pharmacokinetic of L608. The dose escalation design is applied in this study. The sentinel dosing design will be applied for all cohorts.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- L608 Inhalation Solution, Placebo solution
- 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.
L608 Inhalation SolutionDrug
subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo
Placebo solutionDrug
subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo
| Study group | Role | What they receive |
|---|---|---|
| L608 Liposomal inhalation solution | Experimental | Eight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). Receives: Drug: L608 Inhalation Solution |
| Placebo | Experimental | Eight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). Receives: Drug: Placebo solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of dose limiting toxicity (DLT)
The percentage of subjects with dose limiting toxicity (DLT) within 14 days after dosing
Measured: Baseline to Day 14
The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
The percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.
Measured: Baseline to Day 21
Frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
The frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.
Measured: Baseline to Day 21
Secondary outcomes (9)
AUC0-t
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration
Measured: Baseline to 24 hours
AUC0-∞
Area under the plasma concentration-time curve from time 0 to infinity
Measured: Baseline to 24 hours
%AUCextrap
AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC
Measured: Baseline to 24 hours
Cmax
Maximum observed plasma concentration
Measured: Baseline to 24 hours
Tmax
Time to reach the maximum observed plasma concentration
Measured: Baseline to 24 hours
T1/2
Apparent plasma terminal elimination half-life
Measured: Baseline to 24 hours
CL/F
Apparent total plasma clearance
Measured: Baseline to 24 hours
Vz/F
Apparent volume of distribution during the terminal phase
Measured: Baseline to 24 hours
kel
Terminal elimination rate constant
Measured: Baseline to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2023
- Study start30 Aug 2023
- Primary completion2 Sep 2024
- Study completion2 Sep 2024
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Randomized, Placebo-controlled, double-blinded, single ascending dose escalation
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmosa Biopharm Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia) Pty Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05938946
- Sponsor's protocol ID
- PBI L608p1
- Status last verified
- Oct 2024
- First submitted
- 9 Jun 2023
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of L608 for Inhalation in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05938946
- Acronym / sponsor ID
- PBI L608p1
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Pharmosa Biopharm Inc.Industry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia) Pty Limited
- Study start
- 30 Aug 2023 (actual)
- Primary completion
- 2 Sep 2024 (actual)
- Study completion
- 2 Sep 2024 (actual)
- First posted
- 11 Jul 2023 (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.
This is a Phase I, randomized, double-blinded, placebo-controlled single ascending dose, sequential-group study to evaluate the safety, tolerability, and PK of single ascending doses of L608 inhalation in healthy volunteers.
Detailed description
L608 inhalation Solution (L608) is developed by Pharmosa Biopharm Inc. (PBI) as a new liposomal Iloprost formulation for inhalation use in the treatment of patients with PAH (WHO Group 1). As a liposomal formulation of iloprost, L608 is intended to reduce the dosing frequency, as well as provide sustained and selective release along with achieving therapeutically relevant iloprost level. Meanwhile, L608 is expected to mitigate burst release related local irritation and systemic side effects (e.g., hypotension due to plasma peak) in clinical practice.
This Phase I, randomized, double-blinded, placebo-controlled study will be conducted in healthy volunteers in Australia to evaluate the safety, tolerability, and pharmacokinetic of L608. The dose escalation design is applied in this study. The sentinel dosing design will be applied for all cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, Placebo-controlled, double-blinded, single ascending dose escalation
| Arm | Type | Receives |
|---|---|---|
| L608 Liposomal inhalation solution | Experimental | Drug: L608 Inhalation SolutionEight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). |
| Placebo | Experimental | Drug: Placebo solutionEight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women aged between 18 and 65 (inclusive) at the time of Screening visit. Females must not be pregnant or lactating.
- Body Mass Index (BMI) of ≥18.5 and ≤30.0 kg/m2
- Non-smokers or former smokers who have smoked ≤ 100 cigarettes in their lifetime and have not consumed any tobacco or tobacco-containing products for at least 3 months prior to Screening.
- Females must not be pregnant or lactating and must use acceptable, highly effective double contraception from Screening until 3 months after the last dose of the Investigational product.
Key exclusion criteria (13 listed)
- Subjects with contraindications or sensitivity to any components of the study treatment.
- Subjects with medical histories (within 3 months prior to Screening) or ongoing conditions of any clinically significant and/or any other medical conditions which may jeopardize the safety of the subjects and/or effect the results of the study at the Investigator's discretion.
- Subjects with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.
- Subjects who voluntarily participate in this study and sign the informed consent form prior to any study procedures.
- Subjects with histories or active conditions of asthma, sleep apnea, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchiectasis, bronchospasm, and/or reactive airway. Subjects who have had childhood asthma which have resolved as deemed by the PI can be considered.
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 |
|---|---|---|
| L608 Inhalation Solutionsubjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo | Drug | L608 Liposomal inhalation solution |
| Placebo solutionsubjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo | Drug | Placebo |
Primary outcome
The incidence of dose limiting toxicity (DLT)
Time frame: Baseline to Day 14
The percentage of subjects with dose limiting toxicity (DLT) within 14 days after dosing
The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time frame: Baseline to Day 21
The percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.
Frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time frame: Baseline to Day 21
The frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.
9 secondary outcomes
AUC0-t
Time frame: Baseline to 24 hours
AUC0-∞
Time frame: Baseline to 24 hours
%AUCextrap
Time frame: Baseline to 24 hours
Cmax
Time frame: Baseline to 24 hours
Tmax
Time frame: Baseline to 24 hours
T1/2
Time frame: Baseline to 24 hours
CL/F
Time frame: Baseline to 24 hours
Vz/F
Time frame: Baseline to 24 hours
kel
Time frame: Baseline to 24 hours
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 16 Oct 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 L608 Inhalation Solution in people with Pulmonary Arterial Hypertension, run by Pharmosa Biopharm Inc. at 1 site in Australia.
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 4 inclusion and 13 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 16 Oct 2024. 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 Australia. 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?
The incidence of dose limiting toxicity (DLT) (time frame: Baseline to Day 14). The study lists 3 primary outcomes in all. 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 16 Oct 2024.