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Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsules

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ClinicalTrials.gov Identifier: NCT02958696
Recruitment Status : Completed
First Posted : November 8, 2016
Last Update Posted : February 3, 2017
Sponsor:
Information provided by (Responsible Party):
Heptares Therapeutics Limited

Brief 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.

Condition or disease Intervention/treatment Phase
Bioavailability and Pharmacokinetics Drug: HTL0018318 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Arm Intervention/treatment
Active Comparator: HTL0018318 low dose
low dose aqueous solution and/or equivalent low dose capsule
Drug: HTL0018318
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.

Active Comparator: HTL0018318 mid dose
mid dose aqueous solution and/or equivalent mid dose capsule
Drug: HTL0018318
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.

Active Comparator: HTL0018318 high dose
high dose aqueous solution and/or equivalent high dose capsule(s)
Drug: HTL0018318
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.




Primary Outcome Measures :
  1. Maximum plasma concentration (Cmax) of HTL0018318 [ Time Frame: Predose to 168h post dose ]
    Comparison of bioavailability in plasma

  2. Area under the curve (AUC) of HTL0018318 [ Time Frame: Predose to 168h post dose ]
    Comparison of bioavailability in plasma


Secondary Outcome Measures :
  1. Time to maximum concentration (tmax) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in plasma

  2. Half-life (t1/2) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in plasma

  3. Apparent volume of distribution (Vz/F) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in plasma

  4. Apparent clearance (CLp/F) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in plasma

  5. Amount excreted in urine (Ae) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in urine

  6. Fraction excreted in urine (fe/F) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in urine

  7. Clearance in urine (CLr) [ Time Frame: Predose to 168h post dose ]
    Pharmacokinetics in urine

  8. Treatment-emergent adverse events [ Time Frame: Predose up to 28 days post dose ]
    Adverse events

  9. Vital signs [ Time Frame: Predose up to 28 days post dose ]
    Heart rate and blood pressure

  10. Physical examinations [ Time Frame: Predose up to 28 days post dose ]
    Physical examinations

  11. Laboratory safety assessments [ Time Frame: Predose up to 28 days post dose ]
    Hematology

  12. ECG [ Time Frame: Predose up to 28 days post dose ]
    ECG



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female healthy volunteer.
  2. Aged 18-55 years.
  3. A body mass index (Quetelet index) in the range 18.0-34.
  4. 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.
  5. Willingness to comply with the contraception requirements of the trial.
  6. 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.
  7. Willingness to give written consent to have data entered into The Overvolunteering Prevention System.

Exclusion Criteria:

  1. 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.
  2. QTcF outside range 300-450 msec for males, and 300-470 msec for females at resting ECG at screening and baseline.
  3. Family history of unexplained sudden death, or sudden death due to long QT syndrome.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. History of a chronic respiratory condition, such as asthma, recurrent chest infections of chronic obstructive pulmonary disease.
  11. History of epilepsy or seizures.
  12. History of a severe allergy. Non-active hayfever is acceptable.
  13. Surgery (e.g. stomach bypass) or medical condition that might affect absorption, metabolism or elimination of medicines.
  14. Presence or history of severe adverse reaction to any drug.
  15. Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception.
  16. 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).
  17. 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.
  18. Evidence of drug abuse on urine testing.
  19. Positive test for hepatitis B, hepatitis C or HIV.
  20. Positive test for alcohol or smoking before dosing.
  21. Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months.
  22. Loss of more than 500 mL blood during the 3 months before the trial, eg as a blood donor.
  23. Possibility that the volunteer will not cooperate with the requirements of the protocol.
  24. Objection by General Practitioner (GP) to volunteer entering trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02958696


Locations
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United Kingdom
Hammersmith Medicines Research
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Heptares Therapeutics Limited
Investigators
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Principal Investigator: Adeep Puri, MPhil MBBS Hammersmith Medicines Research

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Responsible Party: Heptares Therapeutics Limited
ClinicalTrials.gov Identifier: NCT02958696     History of Changes
Other Study ID Numbers: HTL0018318-104
2016-003313-99 ( EudraCT Number )
16-024 ( Other Identifier: HMR Protocol Code )
First Posted: November 8, 2016    Key Record Dates
Last Update Posted: February 3, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Pharmaceutical Solutions