Pulmonary HypertensionPhase 1NCT04891354
A First-in-Human Study to Assess the Safety and Tolerability of PDNO
A Phase 1 study testing PDNO in people with Pulmonary Hypertension, run by Attgeno AB at 1 site in Sweden.
Trial summary
This is a first-in-human, single-blind, placebo-controlled, single-centre study designed to assess the safety and tolerability of PDNO in healthy male and female subjects. In addition, the exposure of 1,2 propanediol (PD) will be evaluated. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- PDNO
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteSweden
- Study dates
- 2 Feb 2021to 25 May 2022
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to give written informed consent for participation in the study
- Healthy male and female subjects aged 18 to 45 years inclusive at screening
- Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m^2 at screening
- Clinically normal medical history, physical findings, ECG and laboratory values
- Male subjects and women of non-childbearing potential may be included in the study. Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential must use contraceptive methods.
- Women of non-childbearing potential are defined as pre-menopausal females who are sterilised or postmenopausal
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, might interfere with the drug absorption, distribution, metabolism or excretion of the drug or influence the results or the subject's ability to participate in the study
- Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP
- Malignancy within the past 5 years
- Any planned major surgery within the duration of the study
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV)
- Women who are pregnant or who are breast feeding
Show all 32Show fewer
- Known patent foramen ovale or other cardiac phenomenon putting the subject at risk in the study
- Presence of history of Raynaud Syndrome
- After 10 minutes supine rest at the time of screening, any vital sign values outside the following ranges: Systolic blood pressure <90 or >140 mmHg, or Diastolic blood pressure <50 or >90 mmHg, or Pulse <40 or >90 bpm
- Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator
- Known history of migraine or frequent headache of other genesis (in average >1 episode of grade 2 (CTCAE v5.0, headache per week)
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to the local anaesthesia planned to be used in the study
- Known hypersensitivity to propanediol
- Veins unsuitable for CVC and arterial cannula insertion
- Failure to perform the FeNO measurement at screening
- FeNO level ≥ 30 ppb
- Within 1 month prior to Screening received continuous treatment with non-steroidal anti-inflammatory drugs (NSAIDs), novel oral anticoagulants (NOACs), warfarin, clopidogrel, or acetylsalicylic acid
- Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP
- Planned treatment or treatment with another investigational drug within 3 months prior to Day -1
- Current smokers or users of nicotine products
- Positive screen for drugs of abuse or alcohol
- Presence or history of alcohol abuse or excessive intake of alcohol
- Presence or history of drug abuse, as judged by the Investigator
- History of, or current use of, anabolic steroids
- Excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages
- Intake of xanthine and/or taurine containing energy drinks at the day of screening.
- Plasma donation within one month of screening or blood donation
- Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
- Previous confirmed COVID-19 that required hospitalisation
- Signs or symptoms probably consistent with COVID-19 disease within the last 7 days prior to Visit 2 or close contact with confirmed COVID-19 patient within the last 7 days prior to Visit 2, as judged by the Investigator
- Positive result for ongoing SARS-CoV-2 presented at Visit 2
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-Blind, Placebo-Controlled, First-in-Human Study to Assess the Safety and Tolerability of PDNO Administered as an Intravenous Infusion in Healthy Subjects
This is a first-in-human, single-blind, placebo-controlled, single-centre study designed to assess the safety and tolerability of PDNO in healthy male and female subjects. In addition, the exposure of 1,2 propanediol (PD) will be evaluated.
There are 2 parts to the study:
Read more
Part I: single ascending dose (SAD), 7 cohorts, 30 minutes intravenous (i.v.) infusion of placebo followed by 1-hour i.v. infusion of PDNO to assess safety, tolerability and PD exposure in healthy male and female subjects.
Part II: ascending doses of PDNO in 2 cohorts, 30 minutes i.v. infusion of placebo followed by 3 ascending doses of PDNO in cohort 1 and 3 ascending doses of PDNO in cohort 2. The first 2 doses in each cohort will be i.v. infused for 30 minutes whereas the last will be i.v. infused for 3 hours to assess safety, tolerability and PD exposure in healthy male and female subjects.
If indicated by emerging data and recommended by the internal safety review committee (iSRC), 2 additional dose groups/cohorts (4+4 subjects) may be added to Part I and 1 dose group/cohort (4 subjects) may be added to Part II.
- Conditions
- Pulmonary Hypertension
- Being tested
- PDNO, Sodium chloride (placebo)
- Keywords
- Acute Pulmonary Hypertension
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDNODrug
Also called Nitrosooxypropanol
PDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture.
Sodium chloride (placebo)Drug
Also called NaCl
Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)
| Study group | Role | What they receive |
|---|---|---|
| Part I: single ascending dose (SAD) | Experimental | In Part I, each subject will receive a 30 minute i.v. infusion of placebo followed by a 1-hour i.v. infusion of PDNO in parallel with a carrier sodium bicarbonate buffer, the infusion of which will start 5 minutes prior to start of placebo infusion and continue until 15 minutes after end of PDNO infusion. Between the end of placebo infusion and prior to the start of PDNO infusion, there will be a 20-minute stabilisation period with infusion of sodium bicarbonate buffer only. Receives: Drug: PDNO; Drug: Sodium chloride (placebo) |
| Part II: ascending doses of PDNO | Experimental | In Part II, each subject will receive a 30 minute i.v. infusion of placebo followed by 2 x 30 minute infusions of PDNO at 2 ascending dose levels and one 3-hour infusion of PDNO at a third dose level. Receives: Drug: PDNO; Drug: Sodium chloride (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of PDNO following i.v. infusion to healthy volunteers, as measured by incidence of treatment-emergent AEs, SAEs, AESI, changes in vital signs, ECG abnormalities, and laboratory abnormalities.
- Treatment-emergent adverse events (AEs)
- Treatment-emergent serious AEs (SAEs)
- Treatment-emergent AEs of special interest (AESI)
- Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature)
- Treatment-emergent electrocardiogram (ECG) abnormalities
- Treatment-emergent laboratory abnormalities
Measured: Through study completion (i.e., Day 8)
Secondary outcomes (4)
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to time t (AUC0-t)
Measured: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to infinity (AUC0-inf)
Measured: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): maximum plasma concentration (Cmax)
Measured: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): terminal elimination half-life (T1/2)
Measured: During 24 hours from start of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start2 Feb 2021
- Primary completion25 May 2022
- Study completion25 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- In Part I, each subject will receive a 30 minute i.v. infusion of placebo followed by a 1-hour i.v. infusion of PDNO in parallel with a carrier sodium bicarbonate buffer, the infusion of which will start 5 minutes prior to start of placebo infusion and continue until 15 minutes after end of PDNO infusion. Between the end of placebo infusion and prior to the start of PDNO infusion, there will be a 20-minute stabilisation period with infusion of sodium bicarbonate buffer only. In Part II, each subject will receive a 30 minute i.v. infusion of placebo followed by 2 x 30 minute infusions of PDNO at 2 ascending dose levels and one 3-hour infusion of PDNO at a third dose level.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Attgeno AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Folke Sjöberg, MD, Principal investigator, CTC Clinical Trial Consultants AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891354
- Sponsor's protocol ID
- 2019-PDNO-001
- Status last verified
- Jan 2023
- First submitted
- 6 May 2021
- Last updated
- 19 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Blind, Placebo-Controlled, First-in-Human Study to Assess the Safety and Tolerability of PDNO Administered as an Intravenous Infusion in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04891354
- Acronym / sponsor ID
- 2019-PDNO-001
- Conditions
- Pulmonary Hypertension
- Keywords
- Acute Pulmonary Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Attgeno ABIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2021 (actual)
- Primary completion
- 25 May 2022 (actual)
- Study completion
- 25 May 2022 (actual)
- First posted
- 18 May 2021 (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 first-in-human, single-blind, placebo-controlled, single-centre study designed to assess the safety and tolerability of PDNO in healthy male and female subjects. In addition, the exposure of 1,2 propanediol (PD) will be evaluated.
There are 2 parts to the study:
Part I: single ascending dose (SAD), 7 cohorts, 30 minutes intravenous (i.v.) infusion of placebo followed by 1-hour i.v. infusion of PDNO to assess safety, tolerability and PD exposure in healthy male and female subjects.
Part II: ascending doses of PDNO in 2 cohorts, 30 minutes i.v. infusion of placebo followed by 3 ascending doses of PDNO in cohort 1 and 3 ascending doses of PDNO in cohort 2. The first 2 doses in each cohort will be i.v. infused for 30 minutes whereas the last will be i.v. infused for 3 hours to assess safety, tolerability and PD exposure in healthy male and female subjects.
If indicated by emerging data and recommended by the internal safety review committee (iSRC), 2 additional dose groups/cohorts (4+4 subjects) may be added to Part I and 1 dose group/cohort (4 subjects) may be added to Part II.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- In Part I, each subject will receive a 30 minute i.v. infusion of placebo followed by a 1-hour i.v. infusion of PDNO in parallel with a carrier sodium bicarbonate buffer, the infusion of which will start 5 minutes prior to start of placebo infusion and continue until 15 minutes after end of PDNO infusion. Between the end of placebo infusion and prior to the start of PDNO infusion, there will be a 20-minute stabilisation period with infusion of sodium bicarbonate buffer only. In Part II, each subject will receive a 30 minute i.v. infusion of placebo followed by 2 x 30 minute infusions of PDNO at 2 ascending dose levels and one 3-hour infusion of PDNO at a third dose level.
| Arm | Type | Receives |
|---|---|---|
| Part I: single ascending dose (SAD) | Experimental | Drug: PDNO, Drug: Sodium chloride (placebo)In Part I, each subject will receive a 30 minute i.v. infusion of placebo followed by a 1-hour i.v. infusion of PDNO in parallel with a carrier sodium bicarbonate buffer, the infusion of which will start 5 minutes prior to start of placebo infusion and continue until 15 minutes after end of PDNO infusion. Between the end of placebo infusion and prior to the start of PDNO infusion, there will be a 20-minute stabilisation period with infusion of sodium bicarbonate buffer only. |
| Part II: ascending doses of PDNO | Experimental | Drug: PDNO, Drug: Sodium chloride (placebo)In Part II, each subject will receive a 30 minute i.v. infusion of placebo followed by 2 x 30 minute infusions of PDNO at 2 ascending dose levels and one 3-hour infusion of PDNO at a third dose level. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Willing and able to give written informed consent for participation in the study
- Healthy male and female subjects aged 18 to 45 years inclusive at screening
- Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m^2 at screening
- Clinically normal medical history, physical findings, ECG and laboratory values
- Male subjects and women of non-childbearing potential may be included in the study. Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential must use contraceptive methods.
Key exclusion criteria (32 listed)
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, might interfere with the drug absorption, distribution, metabolism or excretion of the drug or influence the results or the subject's ability to participate in the study
- Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP
- Malignancy within the past 5 years
- Any planned major surgery within the duration of the study
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV)
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 |
|---|---|---|
| PDNOAlso: NitrosooxypropanolPDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture. | Drug | Part I: single ascending dose (SAD), Part II: ascending doses of PDNO |
| Sodium chloride (placebo)Also: NaClPlacebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL) | Drug | Part I: single ascending dose (SAD), Part II: ascending doses of PDNO |
Primary outcome
Safety and tolerability of PDNO following i.v. infusion to healthy volunteers, as measured by incidence of treatment-emergent AEs, SAEs, AESI, changes in vital signs, ECG abnormalities, and laboratory abnormalities.
Time frame: Through study completion (i.e., Day 8)
* Treatment-emergent adverse events (AEs) * Treatment-emergent serious AEs (SAEs) * Treatment-emergent AEs of special interest (AESI) * Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature) * Treatment-emergent electrocardiogram (ECG) abnormalities * Treatment-emergent laboratory abnormalities
4 secondary outcomes
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to time t (AUC0-t)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to infinity (AUC0-inf)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): maximum plasma concentration (Cmax)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): terminal elimination half-life (T1/2)
Time frame: During 24 hours from start of dosing
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 19 Jan 2023.
- Individual participant dataSharing planned: No
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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.
Folke Sjöberg, MD principal investigator
CTC Clinical Trial Consultants AB
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 PDNO in people with Pulmonary Hypertension, run by Attgeno AB at 1 site in Sweden.
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 32 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 19 Jan 2023. 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 Sweden. 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?
Safety and tolerability of PDNO following i.v. infusion to healthy volunteers, as measured by incidence of treatment-emergent AEs, SAEs, AESI, changes in vital signs, ECG abnormalities, and laboratory abnormalities. (time frame: Through study completion (i.e., Day 8)). 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 19 Jan 2023.