Bioavailability and PharmacokineticsPhase 1NCT02958696
Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsules
A Phase 1 study testing HTL0018318 in people with Bioavailability and Pharmacokinetics, run by Nxera Pharma UK Limited at 1 site in United Kingdom.
Trial summary
HTL0018318 is a selective muscarinc M1 agonist. This study is a phase I, open label, randomised, crossover, single dose, trial in healthy volunteers to compare the relative bioavailability of HTL0018318 when given by oral aqueous solution and in capsule formulation. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bioavailability and Pharmacokinetics
- What is being tested?
- HTL0018318
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2016to Jan 2017
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female healthy volunteer.
- Aged 18-55 years.
- A body mass index (Quetelet index) in the range 18.0-34.
- Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
- Willingness to comply with the contraception requirements of the trial.
- Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
- Willingness to give written consent to have data entered into The Overvolunteering Prevention System.
Who cannot join
- Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
- QTcF outside range 300-450 msec for males, and 300-470 msec for females at resting ECG at screening and baseline.
- Family history of unexplained sudden death, or sudden death due to long QT syndrome.
- Clinically relevant abnormal findings based on 24 h ECG Holter monitoring during screening, including any of the following: > 200 ventricular ectopic heart beats, ventricular tachycardia, defined as >= 3 successive ventricular ectopic beats at a rate of >120 bpm, second degree heart block, sustained cardiac arrhythmias, including atrial fibrillation, complete heart block and supraventricular tachycardia (SVT), any symptomatic arrhythmia except isolated extra systoles.
- Aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin >1.5 x ULN at screening, or other laboratory blood chemistry test results outside the normal reference range unless deemed not clinically significant by the investigator.
- Clinically significant renal insufficiency as indicated by a glomerular filtration rate lower than the age-related L at screening. In the event of a glomerular filtration rate >80, eligibility may be confirmed by a second measurement.
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- Blood pressure and heart rate in supine position at the screening examination outside the ranges 90-140 mm Hg systolic, 50-90 mm Hg diastolic; heart rate 45-100 beats/min. Subject with borderline values can be included if the values are deemed not clinically significant by the investigator.
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
- Impaired gastrointestinal, endocrine, thyroid, hepatic, cardiovascular, respiratory, haematological, renal or neurological function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness deemed clinically significant by the investigator.
- History of a chronic respiratory condition, such as asthma, recurrent chest infections of chronic obstructive pulmonary disease.
- History of epilepsy or seizures.
- History of a severe allergy. Non-active hayfever is acceptable.
- Surgery (e.g. stomach bypass) or medical condition that might affect absorption, metabolism or elimination of medicines.
- Presence or history of severe adverse reaction to any drug.
- Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception.
- Use of a prescription or over-the-counter medicine, or any herbal remedy or nutritional supplement, during the 21 days before the first dose of trial medication until the end of the study, with the exception of acetaminophen (paracetamol), hormonal contraceptives or hormone replacement therapy (HRT).
- Presence or history of drug or alcohol abuse in the last 5 years, or intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women), or use of cigarettes or nicotine-containing products during the 3 months before the first dose until the end of the study.
- Evidence of drug abuse on urine testing.
- Positive test for hepatitis B, hepatitis C or HIV.
- Positive test for alcohol or smoking before dosing.
- Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months.
- Loss of more than 500 mL blood during the 3 months before the trial, eg as a blood donor.
- Possibility that the volunteer will not cooperate with the requirements of the protocol.
- Objection by General Practitioner (GP) to volunteer entering trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomised, Open Label, 2-period Crossover, Single Centre, 3-arm, Single Dose Study to Investigate the Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsule Formation in Healthy Volunteers
HTL0018318 is a selective muscarinc M1 agonist. This study is a phase I, open label, randomised, crossover, single dose, trial in healthy volunteers to compare the relative bioavailability of HTL0018318 when given by oral aqueous solution and in capsule formulation.
- Conditions
- Bioavailability and Pharmacokinetics
- Being tested
- HTL0018318
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTL0018318Drug
Two single doses of active drug (low, mid or high dose either as aqueous solution or capsule) separated by a washout of at least 12 days.
| Study group | Role | What they receive |
|---|---|---|
| HTL0018318 low dose | Active comparator | low dose aqueous solution and/or equivalent low dose capsule Receives: Drug: HTL0018318 |
| HTL0018318 mid dose | Active comparator | mid dose aqueous solution and/or equivalent mid dose capsule Receives: Drug: HTL0018318 |
| HTL0018318 high dose | Active comparator | high dose aqueous solution and/or equivalent high dose capsule(s) Receives: Drug: HTL0018318 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of HTL0018318
Comparison of bioavailability in plasma
Measured: Predose to 168h post dose
Area under the curve (AUC) of HTL0018318
Comparison of bioavailability in plasma
Measured: Predose to 168h post dose
Secondary outcomes (12)
Time to maximum concentration (tmax)
Pharmacokinetics in plasma
Measured: Predose to 168h post dose
Half-life (t1/2)
Pharmacokinetics in plasma
Measured: Predose to 168h post dose
Apparent volume of distribution (Vz/F)
Pharmacokinetics in plasma
Measured: Predose to 168h post dose
Apparent clearance (CLp/F)
Pharmacokinetics in plasma
Measured: Predose to 168h post dose
Amount excreted in urine (Ae)
Pharmacokinetics in urine
Measured: Predose to 168h post dose
Fraction excreted in urine (fe/F)
Pharmacokinetics in urine
Measured: Predose to 168h post dose
Clearance in urine (CLr)
Pharmacokinetics in urine
Measured: Predose to 168h post dose
Treatment-emergent adverse events
Adverse events
Measured: Predose up to 28 days post dose
Vital signs
Heart rate and blood pressure
Measured: Predose up to 28 days post dose
Physical examinations
Physical examinations
Measured: Predose up to 28 days post dose
Laboratory safety assessments
Hematology
Measured: Predose up to 28 days post dose
ECG
ECG
Measured: Predose up to 28 days post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bioavailability and PharmacokineticsStudies 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nxera Pharma UK Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adeep Puri, MPhil MBBS, Principal investigator, Hammersmith Medicines Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02958696
- Sponsor's protocol ID
- HTL0018318-104
- Other IDs
- 2016-003313-99, 16-024, 2016
- Status last verified
- Feb 2017
- First submitted
- 1 Nov 2016
- Last updated
- 3 Feb 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 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomised, Open Label, 2-period Crossover, Single Centre, 3-arm, Single Dose Study to Investigate the Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsule Formation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02958696
- Acronym / sponsor ID
- HTL0018318-104
- Conditions
- Bioavailability and Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Nxera Pharma UK LimitedIndustry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 8 Nov 2016 (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.
HTL0018318 is a selective muscarinc M1 agonist. This study is a phase I, open label, randomised, crossover, single dose, trial in healthy volunteers to compare the relative bioavailability of HTL0018318 when given by oral aqueous solution and in capsule formulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HTL0018318 low dose | Active comparator | Drug: HTL0018318low dose aqueous solution and/or equivalent low dose capsule |
| HTL0018318 mid dose | Active comparator | Drug: HTL0018318mid dose aqueous solution and/or equivalent mid dose capsule |
| HTL0018318 high dose | Active comparator | Drug: HTL0018318high dose aqueous solution and/or equivalent high dose capsule(s) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female healthy volunteer.
- Aged 18-55 years.
- A body mass index (Quetelet index) in the range 18.0-34.
- Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
- Willingness to comply with the contraception requirements of the trial.
Key exclusion criteria (24 listed)
- Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
- QTcF outside range 300-450 msec for males, and 300-470 msec for females at resting ECG at screening and baseline.
- Family history of unexplained sudden death, or sudden death due to long QT syndrome.
- Clinically relevant abnormal findings based on 24 h ECG Holter monitoring during screening, including any of the following: > 200 ventricular ectopic heart beats, ventricular tachycardia, defined as >= 3 successive ventricular ectopic beats at a rate of >120 bpm, second degree heart block, sustained cardiac arrhythmias, including atrial fibrillation, complete heart block and supraventricular tachycardia (SVT), any symptomatic arrhythmia except isolated extra systoles.
- Aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin >1.5 x ULN at screening, or other laboratory blood chemistry test results outside the normal reference range unless deemed not clinically significant by the investigator.
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 |
|---|---|---|
| HTL0018318Two single doses of active drug (low, mid or high dose either as aqueous solution or capsule) separated by a washout of at least 12 days. | Drug | HTL0018318 high dose, HTL0018318 low dose, HTL0018318 mid dose |
Primary outcome
Maximum plasma concentration (Cmax) of HTL0018318
Time frame: Predose to 168h post dose
Comparison of bioavailability in plasma
Area under the curve (AUC) of HTL0018318
Time frame: Predose to 168h post dose
Comparison of bioavailability in plasma
12 secondary outcomes
Time to maximum concentration (tmax)
Time frame: Predose to 168h post dose
Half-life (t1/2)
Time frame: Predose to 168h post dose
Apparent volume of distribution (Vz/F)
Time frame: Predose to 168h post dose
Apparent clearance (CLp/F)
Time frame: Predose to 168h post dose
Amount excreted in urine (Ae)
Time frame: Predose to 168h post dose
Fraction excreted in urine (fe/F)
Time frame: Predose to 168h post dose
Clearance in urine (CLr)
Time frame: Predose to 168h post dose
Treatment-emergent adverse events
Time frame: Predose up to 28 days post dose
Vital signs
Time frame: Predose up to 28 days post dose
Physical examinations
Time frame: Predose up to 28 days post dose
Laboratory safety assessments
Time frame: Predose up to 28 days post dose
ECG
Time frame: Predose up to 28 days post 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 3 Feb 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.
Adeep Puri, MPhil MBBS principal investigator
Hammersmith Medicines Research
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 HTL0018318 in people with Bioavailability and Pharmacokinetics, 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 7 inclusion and 24 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 3 Feb 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. 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?
Maximum plasma concentration (Cmax) of HTL0018318 (time frame: Predose to 168h post dose). The study lists 2 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 3 Feb 2017.