Comparison of Blood Levels of HTL0016878 From an Oral Capsule and an Oral Solution

• Sponsor: Heptares Therapeutics Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04935320
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 3
• Actual Duration (Months): 3.1
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

This is a randomised, open-label, 3-period, crossover single dose study to assess the relative bioavailability of two formulations of HTL0016878: an oral solution of HCl salt form (the reference product) and an oral capsule containing citrate salt (the test product); and of the effect of food on the pharmacokinetics of the capsule formulation.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: HTL0016878.HCl Solution 10 mg; Drug: HTL0016878.Citrate Capsule 10 mg	Phase 1

Detailed Description

Fifteen healthy male or female subjects will be enrolled. Each subject will have 3 study sessions and receive a single oral dose of 10 mg HTL0016878 on Day 1 of each study session. Subjects will receive the HTL0016878.HCl oral solution in the fasted state in 1 session, and the HTL0016878.citrate capsule, in the fasted state and after a high-fat meal, respectively, in the other 2 sessions. Each subject will be randomised to 1 of 3 treatment sequences (5 subjects to each sequence). There will be a washout of at least 10 days between doses. Subjects will be screened within 35 days before their first dose of HTL0016878. In each study session, subjects will be resident on the ward from the day before dosing (Day -1) until completion of procedures 72 h after their dose (Day 4). Subjects will return for a follow up visit 10-13 days after their final dose of trial medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Randomised, Open-label, 3-period Crossover, Single Dose Study in Healthy Subjects, to Assess Relative Bioavailability From an Oral Capsule of HTL0016878 Citrate Salt Versus an Oral Solution of HTL0016878 Hydrochloride Salt
• Actual Study Start Date: Jul 27, 2021
• Actual Primary Completion Date: Oct 29, 2021
• Actual Study Completion Date: Oct 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Solution Fasted HTL0016878.HCl 10 mg, single dose, oral solution, fasted	Drug: HTL0016878.HCl Solution 10 mg; Oral solution fasted
Experimental: Oral Capsule Fasted HTL0016878.citrate 10 mg, single dose, oral capsule, fasted	Drug: HTL0016878.Citrate Capsule 10 mg; Oral capsule fed or fasted
Experimental: Oral Capsule Fed HTL0016878.citrate 10 mg, single dose, oral capsule, fed	Drug: HTL0016878.Citrate Capsule 10 mg; Oral capsule fed or fasted

Outcome Measures

Primary Outcome Measures

1. Concentration of HTL0016878 in plasma Cmax [0-72 hours]

   Pharmacokinetics

2. Concentration of HTL0016878 in plasma AUC [0-72 hours]

   Pharmacokinetics

Secondary Outcome Measures

1. Treatment Emergent Adverse Events [Baseline up to 13 days post-dose]

   Safety and Tolerability

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy male or females, aged 18-50 years

2. Female subjects must agree to use highly effective contraception

3. Weigh 60 kg or more, with a BMI in the range 18.0-30.0 kg/m2

4. Sufficient intelligence to understand the nature of the trial

5. Willingness to give written consent to participate

6. Agree to use the contraception requirements of the trial

7. Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication

8. Willingness to give written consent to have data entered into The Overvolunteering Prevention System

Exclusion Criteria:

1. Woman who is pregnant or lactating

2. Clinically relevant abnormal history, physical findings, ECG, or laboratory values

3. Presence or history of acute or chronic illness, or mental health problem

4. Impaired neurological, endocrine, thyroid, cardiovascular, respiratory, gastrointestinal, hepatic or renal function, diabetes mellitus, coronary heart disease, or history of any psychiatric disorder or psychotic mental illness

5. Cancer during the 5 years before screening

6. Supine blood pressure and heart rate outside the ranges: 90-140 mm Hg systolic and 50-90 mm Hg diastolic blood pressure; heart rate 45-80 beats/min

7. Supine QT interval (QTcF) outside the ranges 300-450 msec (men) and 300-470 msec (women)

8. Personal or family history of long QT syndrome or family sudden death

9. Positive test for hepatitis B, hepatitis C or HIV

10. Aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase or total bilirubin levels > 1.5 times the upper limit of normal

11. Creatinine clearance < 80 mL/min/1.73 m2

12. Presence or history of drug or alcohol abuse in the past 5 years; or regular intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women); or use of cigarettes, tobacco and/or nicotine-containing products during the 3 months before dosing

13. Evidence of drug abuse or positive alcohol or cotinine test results

14. Positive pregnancy test

15. Habitual and heavy consumption of caffeinated beverages

16. Use of a prescription or over-the-counter medicine, any herbal remedy, or nutritional supplement

17. Receipt of a vaccine against COVID-19 in the 14 days before dosing

18. Received live attenuated vaccination within 6 weeks prior to Screening

19. History of severe allergies

20. Use of any drugs that are inhibitors of CYP2D6

21. Poor metaboliser of CYP2D6

22. History of epilepsy or seizures

23. Any disease associated with cognitive impairment and/or psychosis

24. Suicidal thoughts or ideation, or insomnia

25. Any history of mental illness (including anxiety, depression), which required medical intervention

26. Presence or history of severe adverse reaction to any drug

27. Surgery or medical condition that might affect absorption of medicines

28. Receipt of an investigational product as part of another clinical trial within the 3 months before dosing in this study

29. Receipt of HTL0016878 in a previous clinical trial

30. Loss of more than 400 mL blood during the 3 months before dosing

31. Unwilling to eat a high-fat breakfast

32. Possibility that the volunteer will not cooperate with the requirements of the protocol

33. Objection by GP to volunteer entering trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hammersmith Medicines Research Ltd (HMR)	London		United Kingdom	NW10 7EW

Sponsors and Collaborators

• Heptares Therapeutics Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Heptares Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT04935320
• Other Study ID Numbers: HTL0016878-102; 18-018; 2018-003685-14
• First Posted: Jun 23, 2021
• Last Update Posted: Nov 2, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Heptares Therapeutics Limited: Relative Bioavailability

Study Results

No Results Posted as of Nov 2, 2021