A clinical trial to evaluate the absolute bioavailability and metabolic profile of aticaprant when administered as an oral tablet and a microdose intravenous infusion in healthy participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

27 Sep 2023 → 3 Nov 2023

Decision date (initial)

2023-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen Research & Development, LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others

To investigate the absolute bioavailability of aticaprant in healthy participants after administration of a single dose of 10 mg oral tablet along with a single IV infusion of 100 μg dose of 14C-aticaprant.

Conditions and MedDRA coding

Healthy Adult Participants

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Healthy participants (male or female) between 18 and 55 years of age, inclusive.
2. 2. Healthy on the basis of medical history performed at screening and the physical examination, vital signs, and 12-lead ECG performed at screening and at admission to the study site on Day -1.
3. 3. Healthy on the basis of clinical laboratory tests performed at screening and/or at admission to the study site on Day -1. If the results of the serum chemistry panel, hematology, coagulation, or urinalysis are outside the normal reference ranges, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the Investigator. ALT, AST, ALP, and bilirubin must be within 1.5 times of upper limit of normal range and not clinically significant as assessed by Investigator.
4. 4. Body weight not less than 50 kg and body mass index (BMI; weight [kg]/height2 [m]2) within the range 18.0-29.9 kg/m2 (inclusive).
5. 5. A woman of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]human chorionic gonadotropin [β-hCG]) at screening and a negative urine pregnancy test on Day -1 of Open-label Intervention Phase.
6. 6. A woman must be 1. Not of childbearing potential 2. Of childbearing potential and - Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 30 days after the last dose - the end of relevant systemic exposure. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
7. 7. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of at least 3 months after receiving the last dose of study intervention.
8. 8. During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 3 months) after receiving the last dose of study intervention: 1. A male participant must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person. 2. A male participant who is sexually active with a woman must use a condom. 3. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. 4. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 1 spermatogenesis cycle (defined for the purpose of the study as approximately 3 months) after receiving the last dose of study intervention.
9. 9. Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mm Hg systolic, inclusive, and no higher than 90 mm Hg diastolic at screening and on Day 1 when they are admitted inpatient or prior to dosing on Day 1. If blood pressure is out of range, up to 2 repeated assessments are permitted.
10. 10. A 12-lead ECG consistent with normal cardiac conduction and function, including: • Sinus rhythm • Pulse rate between 40 and 100 bpm, extremes included • QTcF interval 450 ms for men, ≤470 for women (corrected cf. Fridericia 1920; ICH E14 2005) • QRS interval of <120 ms • PR interval <210 ms • Morphology consistent with healthy cardiac conduction and function In addition, the ECG scheduled on Day 1 predose will serve both as eligibility as well as baseline. If anything changes significantly like HR or rhythm from the previous ECG, the participant will not be dosed. At the same point, it will serve as baseline predose to compare postdose ECGs and observe any significant changes.

Exclusion criteria 17

1. 1. History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 60 mL/min based upon MDRD formula, thyroid disease, neurologic or psychiatric disease including Parkinson’s disease, infection, hypertension, vascular disorder, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results.
2. 2. History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence).
3. 3. Known allergies, hypersensitivity, or intolerance to aticaprant or its excipients
4. 4. Has clinically significant abnormal 12-lead ECG, vital signs, or physical examination at screening as assessed by the Investigator.
5. 5. Has a known history (past 6 months) of peptic ulcer, or history (lifetime) of upper gastrointestinal bleeding, or known untreated Helicobacter pylori infection, or a diagnosis of Zollinger Ellison syndrome (ZES). Also, exclude patients with relevant GI surgery that could possibly affect absorption of drug.
6. 6. Had major surgery (eg, requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
7. 7. Has a current homicidal ideation/intent, per the Investigator’s evaluation and clinical judgment, or had suicidal ideation with intent to act within 3 months prior to the start of the Screening Phase, per the Investigator’s clinical judgment or a history of suicidal behavior within the past 6 months prior to the start of the Screening Phase. Participants reporting suicidal ideation with intent to act or suicidal behavior on Day-1 prior to start of the treatment should be excluded.
8. 8. Contraindications to the use of aticaprant or similar class drugs per local prescribing information.
9. 9. Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study intervention.
10. 10. Use of any prescription or nonprescription medication (including vitamins, herbal supplements, and mineral supplements), except for paracetamol/acetaminophen (The use of paracetamol/acetaminophen is allowed until 3 days before the study intervention administration. Throughout the study, a maximum of 3 doses per day of 500 mg paracetamol/acetaminophen and no more than 3 g per week, will be allowed for the treatment of headache or other pain), hormone-based contraceptives, and hormonal replacement therapy, within 14 days before the first dose of the study intervention is scheduled until completion of the study.
11. 11. Received an investigational intervention (including investigational vaccine) or used an invasive investigational medical device within 1 month or within a period less than 5 times the drug’s half-life, if known, whichever is longer, before the planned first dose of study intervention or is currently enrolled in an investigational study.
12. 12. Positive prestudy intervention/alcohol screen.
13. 13. Positive human immunodeficiency virus (HIV) antibody test.
14. 14. Presence of hepatitis B surface antigen (HBsAg) [or hepatitis B core antibody (HBcAb)] at screening or within 3 months prior to first dose of study intervention.
15. 15. Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.
16. 16. Positive hepatitis C RNA test result at screening or within 3 months prior to study intervention.
17. 17. Presence of hepatitis A virus IgM antibody test at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute bioavailability (Fabs).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications