Cystic FibrosisPhase 1NCT02679729
To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration
A Phase 1 study testing AZD5634 for inhalation and AZD5634 for infusion in people with Cystic Fibrosis, run by AstraZeneca at 2 sites in United States.
Trial summary
This is a Phase 1, first-in-human (FIH) single ascending dose study being conducted to better understand the safety, tolerability and pharmacokinetics of AZD5634 in healthy subjects Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- AZD5634 for inhalation and AZD5634 for infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Feb 2016to 24 Oct 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 - 50 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
- Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation.
- Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive.
- Have a FEV1 (Forced expiratory volume in 1 second in liters) ≥ 80% of the predicted value at screening.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research.
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, or influence the results or the subject's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of investigational medicinal product (IMP).
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
- Abnormal vital signs, after 10 minutes supine rest, at screening and check-in, defined as any of the following:
Show all 33Show fewer
- Systolic blood pressure (SBP) < 90mmHg (millimeter of mercury) or ≥ 140 mmHg
- Diastolic blood pressure (DBP) < 50mmHg or ≥ 90 mmHg
- Heart Rate < 45 or > 85 beats per minute (bpm)
- Any clinically significant abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc (QT [ECG interval measured from the onset of the QRS complex to the end of the T wave] interval corrected for heart rate) interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy, at screening.
- PR (PQ [ECG interval measured from the onset of the P wave to the onset of the QRS complex]) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation, at screening.
- Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms. Subjects with QRS (ECG interval measured from the onset of the QRS complex to the J point) > 110 ms but < 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation, at screening.
- Serum/plasma potassium levels are outside the normal range and lower than 3.5 to 5.1 mEq/L (milliequivalents per liter) at screening and prior to dosing.
- Has active lung disease/asthma that requires treatment.
- Known or suspected history of drug abuse, as judged by the investigator.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months.
- History of alcohol abuse or excessive intake of alcohol, as judged by the investigator.
- Positive screen for drugs of abuse, cotinine (nicotine), or alcohol at screening or admission to the unit.
- History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5634.
- Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator.
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the administration of IMP.
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the administration of IMP or longer if the medication has a long half-life.
- Plasma donation within 1 month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the administration of IMP in this study. The period of exclusion is 3 months after the final dose from a previous study.
- Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- Involvement of any Astra Zeneca, PAREXEL or study site employee or their close relatives.
- Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- Subjects who are vegans or have medical dietary restrictions.
- Subjects who cannot communicate reliably with the investigator.
- In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
- Previous bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Research Site
Baltimore, Maryland, 21225
Research Site
Glendale, California, 91206
About this study
Official title: A Phase I, Randomized, Single-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Single-Ascending Inhaled Doses (Part A) and After Single Inhaled and Intravenous Doses (Part B) in Healthy Subjects
This is a Phase 1, first-in-human (FIH) single ascending dose study being conducted to better understand the safety, tolerability and pharmacokinetics of AZD5634 in healthy subjects
Read the detailed description
This study is a Phase I, FIH, randomized, single-blinded (study center staff remain blinded during the dosing phase of the study), placebo-controlled, single ascending dose, sequential dose group study in healthy male subjects and/or female subjects of non-childbearing potential at a single study center to assess AZD5634 following inhaled and intravenous dose administration
- Conditions
- Cystic Fibrosis
- Being tested
- AZD5634 for inhalation, AZD5634 for infusion, Placebo
- Keywords
- inhaled dose, intravenous dose, healthy subjects, safety, tolerability, pharmacokinetics, AZD5634, jet nebulizer
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5634 for inhalationDrug
Solution, citrate buffer, saline nebulizer solution; strength 0.1 - 5 mg/g; administered by jet nebulizer
AZD5634 for infusionDrug
Solution, citrate buffer, saline solution for infusion; strength 0.013 mg/mL
PlaceboOther
inactive substance
| Study group | Role | What they receive |
|---|---|---|
| Part A, Dose Level 1 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 2 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 3 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 4 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 5 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 6 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part A, Dose Level 7 | Experimental | Subjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed Receives: Drug: AZD5634 for inhalation; Other: Placebo |
| Part B, Dose Level 1 | Experimental | Subjects will receive a single dose of IV AZD5634 and after a washout period of 14 days the same subjects will receive a single dose of inhaled AZD5634 Receives: Drug: AZD5634 for infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B).
To assess the safety and tolerability of AZD5634 in terms of number of participants following inhaled administration of single-ascending doses (SAD) (Part A) and following administration of single inhaled and IV doses (Part B)
Measured: Screening (serious adverse event, SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose.
Secondary outcomes (16)
Observed Maximum Plasma Concentration, Taken Directly From the Individual Concentration-time Curve (Cmax)- For Part A and Part B
To assess the pharmacokinetic (PK) parameter Cmax of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Area Under Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part A and Part B
To assess the pharmacokinetic parameter AUC of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. AUC was estimated by AUC(0-last) + Clast/λz where Clast was the last observed quantifiable concentration. AUCs were calculated using the linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. AUC0-t is expanded as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. Note:Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] for Part A and Part B
To assess the pharmacokinetic parameter AUC(0-t) of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Absolute Systemic Bioavailability After Inhalation (Part B Only) (Finhalation,Total)
To assess the Absolute systemic bioavailability after inhalation (%), calculated separately as 100*AUCinhalation*Doseiv/(AUCiv*Doseinhalation)
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Renal Clearance (CLR), Estimated by Dividing Ae(0-last) by AUC0-t - For Part A and Part B
To assess the pharmacokinetic parameter CLR of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: -12-0, 0-6, 6-12, 12-24, 24-48 h (Days 1 to 3)
Cmax, Divided by the Dose Aministered (Cmax/Dose) - For Part A and Part B
To assess the pharmacokinetic parameter Cmax/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Terminal Half-life (t1/2λz), Estimated as (ln2)/λz - For Part A and Part B
To assess the pharmacokinetic parameter t1/2λz of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
AUC0-t, Divided by the Dose Administered (AUC0-t/Dose) - For Part A and Part B
To assess the pharmacokinetic parameter AUC0-t/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
AUC, Divided by the Dose Administered (AUC/Dose) - For Part A and Part B
To assess the pharmacokinetic parameter AUC/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Systemic Clearance for AZD5634 Estimated as Dose Divided by AUC (Part B IV Dosing Only) (CL)
To assess the pharmacokinetic parameter CL of AZD5634 following single-dose IV administration of AZD5634 in Part B
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Apparent Clearance for AZD5634 Estimated as Dose Divided by AUC (Part A and Part B Inhaled Dosing Only) (CL/F)
To assess the pharmacokinetic parameter CL/F of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Mean Residence Time (MRT) - For Part A and Part B
To assess the pharmacokinetic parameter MRT of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Mean Absorption Time, Calculated as MRTinhaled - MRTIV (Part B Only) (MAT)
To assess the pharmacokinetic parameter MAT of AZD5634 following single-dose IV or inhalation administration of AZD5634 in Part B
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Volume of Distribution for AZD5634 at Steady State (IV Administration), Estimated by Dividing the MRT by the Systemic CL (Part B IV Dosing Only) (Vss)
To assess the pharmacokinetic parameter Vss of AZD5634 following single-dose IV administration of AZD5634 in Part B
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Volume of Distribution for AZD5634 at Terminal Phase (IV Administration), Estimated by Dividing the Systemic CL by λz (Part B IV Dosing Only) (Vz)
To assess the pharmacokinetic parameter Vz of AZD5634 following single-dose IV administration of AZD5634 in Part B
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Apparent Volume of Distribution for AZD5634 at Terminal Phase (Inhaled Administration), Estimated by Dividing the CL/F by λz (Part A and Part B Inhaled Dosing Only) (Vz/F)
To assess the pharmacokinetic parameter Vz/F of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Measured: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study start11 Feb 2016
- Primary completion24 Oct 2016
- Study completion24 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ronald Goldwater, MDCM, M.Sc, CPI, Principal investigator, PAREXEL Early Phase Clinical Unit Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679729
- Sponsor's protocol ID
- D6600C00001
- Status last verified
- Mar 2018
- First submitted
- 3 Feb 2016
- Last updated
- 5 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kristensson C, Astrand A, Donaldson S, Goldwater R, Abdulai R, Patel N, Gardiner P, Tehler U, Mercier AK, Olsson M, Ersdal E, Maenpaa J, Bramer T, Malmgren A, Bennett W, Keen C. AZD5634, an inhaled ENaC inhibitor, in healthy subjects and patients with cystic fibrosis. J Cyst Fibros. 2022 Jul;21(4):684-690. doi: 10.1016/j.jcf.2022.02.010. Epub 2022 Feb 26.
PubMed 35227647
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Single-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Single-Ascending Inhaled Doses (Part A) and After Single Inhaled and Intravenous Doses (Part B) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02679729
- Acronym / sponsor ID
- D6600C00001
- Conditions
- Cystic Fibrosis
- Keywords
- inhaled dose, intravenous dose, healthy subjects, safety, tolerability, pharmacokinetics, AZD5634, jet nebulizer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2016 (actual)
- Primary completion
- 24 Oct 2016 (actual)
- Study completion
- 24 Oct 2016 (actual)
- First posted
- 10 Feb 2016 (estimated)
- Results
- Posted 5 Nov 2018
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 1, first-in-human (FIH) single ascending dose study being conducted to better understand the safety, tolerability and pharmacokinetics of AZD5634 in healthy subjects
Detailed description
This study is a Phase I, FIH, randomized, single-blinded (study center staff remain blinded during the dosing phase of the study), placebo-controlled, single ascending dose, sequential dose group study in healthy male subjects and/or female subjects of non-childbearing potential at a single study center to assess AZD5634 following inhaled and intravenous dose administration
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part A, Dose Level 1 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 2 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 3 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 4 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 5 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 6 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part A, Dose Level 7 | Experimental | Drug: AZD5634 for inhalation, Other: PlaceboSubjects will inhale single doses of AZD5634 or placebo under fasted conditions and will rinse his/her mouth with approximately 100 mL (up to 240 mL) of water which must be swallowed |
| Part B, Dose Level 1 | Experimental | Drug: AZD5634 for infusionSubjects will receive a single dose of IV AZD5634 and after a washout period of 14 days the same subjects will receive a single dose of inhaled AZD5634 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 - 50 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
- Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive.
- Have a FEV1 (Forced expiratory volume in 1 second in liters) ≥ 80% of the predicted value at screening.
Key exclusion criteria (33 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, or influence the results or the subject's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of investigational medicinal product (IMP).
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), 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 |
|---|---|---|
| AZD5634 for inhalationSolution, citrate buffer, saline nebulizer solution; strength 0.1 - 5 mg/g; administered by jet nebulizer | Drug | Part A, Dose Level 1, Part A, Dose Level 2, Part A, Dose Level 3, Part A, Dose Level 4, Part A, Dose Level 5, Part A, Dose Level 6, Part A, Dose Level 7 |
| AZD5634 for infusionSolution, citrate buffer, saline solution for infusion; strength 0.013 mg/mL | Drug | Part B, Dose Level 1 |
| Placeboinactive substance | Other | Part A, Dose Level 1, Part A, Dose Level 2, Part A, Dose Level 3, Part A, Dose Level 4, Part A, Dose Level 5, Part A, Dose Level 6, Part A, Dose Level 7 |
Primary outcome
Safety and Tolerability of AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B).
Time frame: Screening (serious adverse event, SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose.
To assess the safety and tolerability of AZD5634 in terms of number of participants following inhaled administration of single-ascending doses (SAD) (Part A) and following administration of single inhaled and IV doses (Part B)
16 secondary outcomes
Observed Maximum Plasma Concentration, Taken Directly From the Individual Concentration-time Curve (Cmax)- For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Area Under Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] for Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Absolute Systemic Bioavailability After Inhalation (Part B Only) (Finhalation,Total)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Renal Clearance (CLR), Estimated by Dividing Ae(0-last) by AUC0-t - For Part A and Part B
Time frame: -12-0, 0-6, 6-12, 12-24, 24-48 h (Days 1 to 3)
Cmax, Divided by the Dose Aministered (Cmax/Dose) - For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Terminal Half-life (t1/2λz), Estimated as (ln2)/λz - For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
AUC0-t, Divided by the Dose Administered (AUC0-t/Dose) - For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
AUC, Divided by the Dose Administered (AUC/Dose) - For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Systemic Clearance for AZD5634 Estimated as Dose Divided by AUC (Part B IV Dosing Only) (CL)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Apparent Clearance for AZD5634 Estimated as Dose Divided by AUC (Part A and Part B Inhaled Dosing Only) (CL/F)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Mean Residence Time (MRT) - For Part A and Part B
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Mean Absorption Time, Calculated as MRTinhaled - MRTIV (Part B Only) (MAT)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Volume of Distribution for AZD5634 at Steady State (IV Administration), Estimated by Dividing the MRT by the Systemic CL (Part B IV Dosing Only) (Vss)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Volume of Distribution for AZD5634 at Terminal Phase (IV Administration), Estimated by Dividing the Systemic CL by λz (Part B IV Dosing Only) (Vz)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Apparent Volume of Distribution for AZD5634 at Terminal Phase (Inhaled Administration), Estimated by Dividing the CL/F by λz (Part A and Part B Inhaled Dosing Only) (Vz/F)
Time frame: At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35227647Kristensson C, Astrand A, Donaldson S, Goldwater R, Abdulai R, Patel N, Gardiner P, Tehler U, Mercier AK, Olsson M, Ersdal E, Maenpaa J, Bramer T, Malmgren A, Bennett W, Keen C. AZD5634, an inhaled ENaC inhibitor, in healthy subjects and patients with cystic fibrosis. J Cyst Fibros. 2022 Jul;21(4):684-690. doi: 10.1016/j.jcf.2022.02.010. Epub 2022 Feb 26.
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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.
Ronald Goldwater, MDCM, M.Sc, CPI principal investigator
PAREXEL Early Phase Clinical Unit Baltimore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD5634 for inhalation and AZD5634 for infusion in people with Cystic Fibrosis, run by AstraZeneca at 2 sites 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 8 inclusion and 33 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 5 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 5 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B). (time frame: Screening (serious adverse event, SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02679729, which also lists 1 linked publication.
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 5 Nov 2018.