Alzheimer's DiseasePhase 1NCT02291783
Phase I, Healthy Subject, Safety, Tolerability and Pharmacokinetic Study of an M1 Agonist to Treat Cognitive Impairment
A Phase 1 study testing HTL0009936 in people with Alzheimer's Disease, run by Nxera Pharma UK Limited at 1 site in United Kingdom.
Trial summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- HTL0009936
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2013to Jul 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index of ≥19 and ≤ 30kg/m²
- Healthy subject free from any clinically significant illness or disease
- Female subjects must be ≥65 years
Who cannot join
- Subject who is predicted to be a CYP2D6 poor or ultra rapid metabolizer
- History of hypersensitivity to study drug
- History of epilepsy or seizures
- Subject with previous history of suicidal behavior
- Subjects with significant hearing impairment
- Subjects with an abnormal EEG
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Parexel Early Phase Clinical Unit
Harrow, Middlesex, HA1 3UJ
About this study
Official title: A Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of HTL0009936 in Healthy Subjects
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders.
Read the detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders. This study is a single ascending dose study.
- Conditions
- Alzheimer's Disease
- Being tested
- HTL0009936, HTL0009936 placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTL0009936Drug
Also called 9936, HTL0009936
Single dose
HTL0009936 placeboDrug
Also called Placebo
Placebo single dose
| Study group | Role | What they receive |
|---|---|---|
| HTL0009936 | Experimental | HTL0009936 single and multiple ascending oral doses. Receives: Drug: HTL0009936 |
| HTL0009936 Placebo | Placebo comparator | HTL0009936 matching placebo Receives: Drug: HTL0009936 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events, as a measure of safety and tolerability
AE reports include a description of the AE, date and time of onset and resolution, intensity, and relationship to IMP.
Measured: From signing of informed consent up to 30 days after the final visit
Changes in Safety Lab parameters as a measure of safety and tolerability
Hematology, clinical chemistry, urinalysis
Measured: Screening, Day-1, at select dosing days, and at 5 to 7 days post dose for single doseand 15 to 17 days post first dose in multiple dosing.
Changes in vital signs as a measure of safety and tolerability
Pulse rate,body temperature,blood pressure, and orthostatic changes.
Measured: Screening, Day-1, at select dosing days and at 5 to 7 days post dose for single dose, and 15 to 17 days post first dose in multiple dosing.
Changes in 12-lead electrocardiograms as a measure of safety and tolerability
Change in ECG parameters
Measured: Screening, pre-dose, at select dosing days and at 5 to 7 days post dose for single dose,and 15 to 17 days post first dose in multiple dosing.
Secondary outcomes (7)
Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax)
Peak plasma concentration (Cmax), time at occurrence of Cmax (tmax), Area under the plasma concentration versus time curve (AUC) 0-t, 0- infinity, percent of AUC 0-infinity, Cmax normalized by dose, AUC 0-t normalized for dose.
Measured: Pre-dose, multiple time points to 24h, at select dosing days, and 5 to 7 days post dosefor single dose,and 15 to 17 days post first dose in multiple dosing.
Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF)
Maximum observed CSF concentration (Cmax CSF), area under the CSF concentration versus time
Measured: Part 1 - 1h, 2h,3h post dose
Pharmacokinetic measures to assess the food effect as measured by ANOVA
Food effect analysis will be based on analysis of variance (ANOVA) for treatment differences.
Measured: Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose.
Pharmacodynamic response as measured by pupillometry
Changes in average pupil diameter as measured in 3 different conditions of lux.
Measured: Multiple time points Day1 to 6h post dose Part 1 only.
Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals
Amount excreted in urine at each collection interval (Ae1-t2) all parts. Cumulative amount excreted to 12h and 24h (Ae0-t) depending on Part. Cumulative urine excreted of unchanged drug to 24h (Fe%) and to 12h depending on Part. Volume of urine collected during each collection interval (Vur), and renal clearance (CLr) all parts
Measured: Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing.
Pharmacodynamic response as measured by Bond and Lader visual analogue scale
Changes in 3 factor scores (Alertness, Contentedness and Calmness) which will be derived from the individual VAS scores
Measured: Day 1 at multiple timepoints to 24h post dose.
Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP)
qEEg and ERP (P50 sensory gating, Mismatch Negativity and P300)
Measured: Screening, Day-1, Day 4, Day 9 multiple dosing regimen only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2014 (estimated)
- Study startNov 2013
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nxera Pharma UK Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Annelize Koch, MBChB, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02291783
- Sponsor's protocol ID
- 9936-101
- Other IDs
- 2013-002307-34
- Status last verified
- Jun 2017
- First submitted
- 7 Oct 2014
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of HTL0009936 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02291783
- Acronym / sponsor ID
- 9936-101
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Nxera Pharma UK LimitedIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 14 Nov 2014 (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.
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders.
Detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in young and elderly healthy volunteers of HTL9936, a selective M1 receptor agonist intended for the treatment of cognitive disorders. This study is a single ascending dose study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HTL0009936 | Experimental | Drug: HTL0009936HTL0009936 single and multiple ascending oral doses. |
| HTL0009936 Placebo | Placebo comparator | Drug: HTL0009936 placeboHTL0009936 matching placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Body mass index of ≥19 and ≤ 30kg/m²
- Healthy subject free from any clinically significant illness or disease
- Female subjects must be ≥65 years
Key exclusion criteria (6 listed)
- Subject who is predicted to be a CYP2D6 poor or ultra rapid metabolizer
- History of hypersensitivity to study drug
- History of epilepsy or seizures
- Subject with previous history of suicidal behavior
- Subjects with significant hearing impairment
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 |
|---|---|---|
| HTL0009936Also: 9936, HTL0009936Single dose | Drug | HTL0009936 |
| HTL0009936 placeboAlso: PlaceboPlacebo single dose | Drug | HTL0009936 Placebo |
Primary outcome
Number of participants with Adverse Events, as a measure of safety and tolerability
Time frame: From signing of informed consent up to 30 days after the final visit
AE reports include a description of the AE, date and time of onset and resolution, intensity, and relationship to IMP.
Changes in Safety Lab parameters as a measure of safety and tolerability
Time frame: Screening, Day-1, at select dosing days, and at 5 to 7 days post dose for single doseand 15 to 17 days post first dose in multiple dosing.
Hematology, clinical chemistry, urinalysis
Changes in vital signs as a measure of safety and tolerability
Time frame: Screening, Day-1, at select dosing days and at 5 to 7 days post dose for single dose, and 15 to 17 days post first dose in multiple dosing.
Pulse rate,body temperature,blood pressure, and orthostatic changes.
Changes in 12-lead electrocardiograms as a measure of safety and tolerability
Time frame: Screening, pre-dose, at select dosing days and at 5 to 7 days post dose for single dose,and 15 to 17 days post first dose in multiple dosing.
Change in ECG parameters
7 secondary outcomes
Pharmacokinetic measures in plasma as measured by Peak plasma concentration (Cmax)
Time frame: Pre-dose, multiple time points to 24h, at select dosing days, and 5 to 7 days post dosefor single dose,and 15 to 17 days post first dose in multiple dosing.
Pharmacokinetic measures in cerebro spinal fluid (CSF) in young males as measured by max observed CSF (Cmax CSF)
Time frame: Part 1 - 1h, 2h,3h post dose
Pharmacokinetic measures to assess the food effect as measured by ANOVA
Time frame: Pre-dose, multiple time points to 24h, and at 12h, 24h and 5 to 7 days post dose.
Pharmacodynamic response as measured by pupillometry
Time frame: Multiple time points Day1 to 6h post dose Part 1 only.
Pharmacokinetic measures in urine in young males and elderly male and female subjects as measured by amount of urine excreted at collection intervals
Time frame: Pre-dose,multiple 4h collection intervals to 24h post dose on select dosing days to Day 10 for multiple dosing.
Pharmacodynamic response as measured by Bond and Lader visual analogue scale
Time frame: Day 1 at multiple timepoints to 24h post dose.
Pharmacodynamic response as measured by changes in qEEG and Event Related Potentials (ERP)
Time frame: Screening, Day-1, Day 4, Day 9 multiple dosing regimen only
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 20 Jun 2017.
- 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.
Annelize Koch, MBChB principal investigator
Parexel
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 HTL0009936 in people with Alzheimer's Disease, run by Nxera Pharma UK Limited 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 3 inclusion and 6 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 20 Jun 2017. 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?
Number of participants with Adverse Events, as a measure of safety and tolerability (time frame: From signing of informed consent up to 30 days after the final visit). The study lists 4 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 20 Jun 2017.