Safety,Phase 1NCT01818869
To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses AZD8848 in Healthy Subjects
A Phase 1 study testing AZD8848 in people with Safety, and Tolerability,, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 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
- Safety,, Tolerability,, Healthy Subjects
- What is being tested?
- AZD8848
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2014to Feb 2014
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and/or female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture
- Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive for at least 3 months prior to Screening and be willing to continue on the chosen contraceptive with additonal use of condom until 3 months postdose
- Male subjects should be willing to use barrier contraception ie, condoms, from the first day of investigational product administration until 3 months after the last administration of investigational product
- Have a body mass index (BMI) between 18 and 32 kg/m2 and weigh at least 50 kg and no more than 110 kg
- Women must have a negative pregnancy test at screening and on admission to the study centre, must have a date of last menstruation, must not be lactating or must be of non-childbearing potential
Who cannot join
- Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: SBP >140 mmHg, Diastolic blood pressure (DBP) >90 mmHg, Heart rate <40 or >85 beats per minute
- History of asthma or allergic rhinitis
- Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome
- 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 as AZD8848 - Any clinically significant abnormalities in clinical chemistry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects
This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 in healthy subjects.
Read the detailed description
A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics after Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects
- Conditions
- Safety,, Tolerability,, Healthy Subjects
- Being tested
- AZD8848, Placebo to match AZD8848
- Keywords
- Safety,, tolerability,, Phase I,, pharmacokinetic,, pharmacodynamic,, inhaled
- Medical subject headings
- Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8848Drug
Multiple doses inhaled IMP via a nebulizer
Placebo to match AZD8848Drug
Multiple doses inhaled matching placebo via a nebulizer
| Study group | Role | What they receive |
|---|---|---|
| AZD8848 | Experimental | Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. Receives: Drug: AZD8848 |
| Placebo to match AZD8848 | Placebo comparator | Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo. In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. Receives: Drug: Placebo to match AZD8848 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline up to 77 days in safety variables (adverse events, vital signs, body temperature, physical exams, ECGs, clinical laboratory tests, pulse oximetry, spirometry).
Measured: From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.
Secondary outcomes (3)
Single dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma and urine from healthy subjects
PK parameters: Cmax, tmax, area under the plasma concentration-time curve from zero to 24 hours postdose (AUC(0-24)), from zero to the time of the last quantifiable concentration (AUC(0-t)) and from zero to infinity (AUC), CL/F, Vz/F, CLR and Ae
Measured: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose. Urine: From days 1 and 22, pre-dose, 0 to 6, 6 to 12 and 12 to 24 hrs post dose
Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma
PK parameters: AUC accumulation ratio and Cmax accumulation ratio
Measured: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose
Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma
Pharmacodynamic effect: CXCL10 concentration and change-from-baseline ratios in plasma
Measured: From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2013 (estimated)
- Study startJan 2014
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Safety,Studies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM, Principal investigator, Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UKAray Aggarwal, Study chair, AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01818869
- Sponsor's protocol ID
- D0542C00002
- Status last verified
- Aug 2015
- First submitted
- 18 Mar 2013
- Last updated
- 14 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Delaney S, Biffen M, Maltby J, Bell J, Asimus S, Aggarwal A, Kraan M, Keeling D. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113. doi: 10.1136/bmjresp-2015-000113. eCollection 2016.
PubMed 26933507
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01818869
- Acronym / sponsor ID
- D0542C00002
- Conditions
- Safety,, Tolerability,, Healthy Subjects
- Keywords
- Safety,, tolerability,, Phase I,, pharmacokinetic,, pharmacodynamic,, inhaled
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 27 Mar 2013 (estimated)
- 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 study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 in healthy subjects.
Detailed description
A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics after Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD8848 | Experimental | Drug: AZD8848Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. |
| Placebo to match AZD8848 | Placebo comparator | Drug: Placebo to match AZD8848Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo. In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male and/or female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture
- Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive for at least 3 months prior to Screening and be willing to continue on the chosen contraceptive with additonal use of condom until 3 months postdose
- Male subjects should be willing to use barrier contraception ie, condoms, from the first day of investigational product administration until 3 months after the last administration of investigational product
- Have a body mass index (BMI) between 18 and 32 kg/m2 and weigh at least 50 kg and no more than 110 kg
- Women must have a negative pregnancy test at screening and on admission to the study centre, must have a date of last menstruation, must not be lactating or must be of non-childbearing potential
Key exclusion criteria (4 listed)
- Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: SBP >140 mmHg, Diastolic blood pressure (DBP) >90 mmHg, Heart rate <40 or >85 beats per minute
- History of asthma or allergic rhinitis
- Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome
- 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 as AZD8848 - Any clinically significant abnormalities in clinical chemistry.
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 |
|---|---|---|
| AZD8848Multiple doses inhaled IMP via a nebulizer | Drug | AZD8848 |
| Placebo to match AZD8848Multiple doses inhaled matching placebo via a nebulizer | Drug | Placebo to match AZD8848 |
Primary outcome
Change from baseline up to 77 days in safety variables (adverse events, vital signs, body temperature, physical exams, ECGs, clinical laboratory tests, pulse oximetry, spirometry).
Time frame: From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.
3 secondary outcomes
Single dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma and urine from healthy subjects
Time frame: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose. Urine: From days 1 and 22, pre-dose, 0 to 6, 6 to 12 and 12 to 24 hrs post dose
Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma
Time frame: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose
Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma
Time frame: From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose.
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 14 Aug 2015.
- Derived from this study: PubMed 26933507Delaney S, Biffen M, Maltby J, Bell J, Asimus S, Aggarwal A, Kraan M, Keeling D. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113. doi: 10.1136/bmjresp-2015-000113. eCollection 2016.
- Study SynopsisLink provided by the sponsor.
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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.
Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM principal investigator
Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UK
Aray Aggarwal study chair
AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States
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 AZD8848 in people with Safety, and Tolerability,, run by AstraZeneca at 1 site in United Kingdom.
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 5 inclusion and 4 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 14 Aug 2015. 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 Kingdom. 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. Some participants in this study may receive a placebo. 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?
Change from baseline up to 77 days in safety variables (adverse events, vital signs, body temperature, physical exams, ECGs, clinical laboratory tests, pulse oximetry, spirometry). (time frame: From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.). 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 NCT01818869, 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 14 Aug 2015.