A six-way relative bioavailability study comparing 10, 30, 40 and 50 mg leniolisib film coated tablets and 30 mg film coated granules with 70 mg film coated tablet in healthy volunteers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharming Technologies B.V.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Mar 2024 → 26 May 2024

Decision date (initial)

2024-02-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To determine the relative bioavailability (relBA) of the 10 mg leniolisib film-coated tablets versus the 70 mg leniolisib film-coated tablets both administered as a single dose.
To determine the relBA of the 30 mg leniolisib film-coated tablets versus the 70 mg leniolisib film-coated tablets both administered as a single dose.
To determine the relBA of the 40 mg leniolisib film-coated tablets versus the 70 mg leniolisib film-coated tablets both administered as a single dose.
To determine the relBA of the 50 mg leniolisib film-coated tablets versus the 70 mg leniolisib film-coated tablets both administered as a single dose.
To determine the relBA of 30 mg leniolisib film-coated granules versus the 70 mg leniolisib film-coated tablets both administered as a single dose.
To evaluate the tolerability of leniolisib after all six single dose treatments.

Conditions and MedDRA coding

Activated Phosphoinositide 3-Kinase Delta Syndrome

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency

EMA paediatric investigation plan (PIP)

EMEA-002989-PIP01-21

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Male or female between 18 and 60 years of age (both inclusive) at the screening visit; female subjects must be of nonchildbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year postmenopausal [amenorrhea duration of 12 consecutive months]) and have a negative serum pregnancy test at screening and a negative urine pregnancy test at (each) admission to the clinical research center.
2. 11. Ability and willingness to abstain from alcohol from 48 hours (2 days) prior to screening and each admission to the clinical research center;
3. 12. Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) and grapefruit (juice) from 48 hours (2 days) prior to screening and each admission to the clinical research center;
4. 13. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
5. 2. Body mass index (BMI) between 18.5 and 30.0 kg/m2 (both inclusive);
6. 3. Subject is judged to be in good health based on medical history, physical examination, vital sign measurements (pulse rate between 50 and 90 bpm), and laboratory safety tests performed at the screening visit and prior to administration of the initial dose of study drug;
7. 5. For this study, a fertile male subject must be abstinent, or must agree to use a condom together with a highly effective method of contraception by the female partner of childbearing potential, when sexually active from first admission to the clinical research center until 3 months (90 days) after the last dose. Highly effective methods of contraception to be used by female partners are the following: - Hormonal contraception that inhibits ovulation: combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectables or implants) - Intrauterine device or intrauterine hormone-releasing system - Bilateral tubal occlusion of the female partner performed at least 3 months prior to the Screening Visit Notes: Sperm donation is not allowed from first admission to the clinical research center until 3 months (90 days) after the last dose. Subjects who practice true abstinence, because of the subject’s lifestyle choice (i.e., the subject should not become abstinent just for the purpose of study participation), are exempt from contraceptive requirements. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. If a subject who is abstinent at the time of signing the informed consent form (ICF) becomes sexually active, they must agree to use contraception as described. Not required of contraception are: - Female who is premenarchal - Female who is postmenopausal, defined as having 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or having had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment, is she considered not of child-bearing potential.
8. 6. No clinically significant abnormality on 12-lead electrocardiogram (ECG) performed at screening;
9. 7. Willing to comply with all study related procedures and restrictions;
10. 8. Subject is a non -smoker or previous smoker who stopped smoking more than 3 months ago;
11. 9. All prescribed medication must have been stopped at least 30 days prior to admission in treatment period 1 to the clinical research center;
12. 10. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g., St. John’s wort) must have been stopped at least 14 days prior to admission in treatment period 1 to the clinical research center. An exception is made for paracetamol, which is allowed up to admission to the clinical research center;
13. 4. No abnormal liver function tests defined as the following: a) Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 1.1 x upper limit of normal (ULN); b) Total bilirubin ≤1.5 × ULN; subjects with a history of Gilbert’s syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is not greater than 0.5 mg/dL.

Exclusion criteria 17

1. Employee of the contract research organization (CRO) or the Sponsor;
2. History of known sensitivity or intolerability to leniolisib or to any related compound or excipients in the formulations, or history of significant multiple and/or severe allergies (including latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food;
3. History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, neoplastic or genitourinary abnormalities or diseases;
4. Subject has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study;
5. Any surgical (e.g., gastrectomy, bariatric surgery, small bowel or large bowel resection) or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug;
6. Subject is mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last year;
7. Subject is unable to refrain from or anticipates the use of any medication throughout the study;
8. Subject consumes excessive amounts of alcohol, defined as greater than 12 g (females) and 24 g (males) alcohol per day, which is equivalent to 7 (females) and 14 (males) glasses of alcoholic beverages per week (1 glass is approximately equivalent to: beer (284 mL), wine (125 mL), or distilled spirits (25 mL);
9. Subject is currently a regular user (including “recreational use”) of any illicit drugs or has a history of drug (including alcohol) abuse within the past year;
10. Subject has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 3 months prior to the screening visit;
11. Exposure to any investigational drug within 90 days of the screening visit;
12. Participation in more than 4 other clinical studies in the 12 months prior to (the first) drug administration in the current study;
13. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (HCVab), or human immunodeficiency virus (HIV) 1 and 2 antibodies;
14. Unsuitable veins for blood sampling;
15. Significant and/or acute illness within 5 days prior to drug administration that may impact safety assessments, in the opinion of the Investigator;
16. There is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason, the investigator considers the subject inappropriate for participation in the study;
17. Any vaccination within 14 days prior to first dosing or scheduled before the follow-up.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The ratio of geometric least square means between the five test formulations and the reference formulation for: • Dose normalized maximum observed drug concentration (Cmax); • Dose normalised area under the concentration versus time curve (AUC) from time zero to the last time point with a measurable concentration (AUC0-tlast); • Dose normalised AUC from time zero to infinity (AUC0-∞)

Secondary endpoints 1

1. Incidence of treatment-emergent adverse events (TEAEs) comparison between the five test formulations and the reference formulation.

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharming Technologies B.V.

Sponsor organisation

Pharming Technologies B.V.

Address

Darwinweg 24

City

Leiden

Postcode

2333 CR

Country

Netherlands

Scientific contact point

Organisation

Pharming Technologies B.V.

Contact name

Clinical Department

Public contact point

Organisation

Pharming Technologies B.V.

Contact name

Clinical Department

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