A Food Effect Study of ZN-d5 in Healthy Female Volunteers

An Open-Label Food Effect Study of ZN-d5 in Healthy Female Volunteers

This is a single-center, sequential, open-label, food effect study to determine the comparative bioavailability of ZN-d5 under fasting and fed conditions, following single-dose oral administration of ZN-d5. The study will be comprised of a pre-study screening, followed by administration of a single dose of ZN-d5 under fasted conditions, a washout period, administration of a single dose of ZN-d5 under fed conditions, and a follow-up period.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ZN-d5

Detailed Description

This is a single-center, sequential, open-label, food effect study to determine the comparative bioavailability of ZN-d5 under fasting and fed conditions, following single-dose oral administration of ZN-d5. The study will be comprised of a pre-study screening, followed by administration of a single dose of ZN-d5 under fasted conditions, a washout period, administration of a single dose of ZN-d5 under fed conditions, and a follow-up period.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anthony Fiorino, MD, PhD; Phone Number: 8582634333; Email: info@zenopharma.com

Study Locations

• New Zealand
  • Christchurch, New Zealand
    • Site # 2801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy females, age 18-65 years;
2. Body mass index (BMI) ≥ 18.0 and ≤ 29.9 kg/m2 and weight ≥ 50 kg and ≤ 100 kg at Screening;
3. Non-smoker and must not have used any tobacco products within two months prior to Screening, or if a smoker, must be currently (and for the last two months prior to screening) smoking ≤ 2 cigarettes or equivalent per week. Participants must be willing to abstain from the use of tobacco and products containing nicotine from 14 days prior to administration of study drug for the duration of the study;
4. No relevant dietary restrictions; willing to consume a high calorie, high fat breakfast and other standard meals provided during the domiciled periods of the study, to comply with the fasting conditions required by the study design, and to avoid consumption of grapefruit, carambola (star fruit), pomelo or Seville oranges or their juices or extracts from 7 days prior to the administration of study drug and for the duration of the study;
5. Willing to abstain from alcohol beginning 48 hours prior to each admission until discharge from the study center at the end of each domiciled period;
6. Able to take and retain oral medications;
7. If sexually active and of childbearing potential, must agree to use two effective methods of contraception beginning at the Screening Visit until 60 days following the last dose of study drug; egg donation is also prohibited during this period (see Appendix 14.1). Post-menopausal status to be confirmed with serum follicle-stimulating hormone (FSH) levels;
8. Negative serum pregnancy test; i.e., beta-human chorionic gonadotropin (β-hCG) test at Screening and negative urine pregnancy test prior to administration of study drug (unless post-menopausal status is FSH-confirmed);
9. Must have the ability and willingness to attend the necessary visits to the study center and to be domiciled overnight where required;
10. Provides written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures;
11. Baseline B lymphocyte count >150 cells/µL (0.15 x109 cells/L).

Exclusion Criteria:

1. Any condition possibly affecting drug absorption (e.g., gastrectomy, gastric banding, or gastric bypass);
2. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant or make it unlikely that the participant will comply with the protocol or complete the study per protocol;
3. Blood donation or significant blood loss within 60 days prior to the first study drug administration or plasma donation within 7 days of the administration of study drug;
4. Routine consumption of xanthine-containing products or foods exceeds 800 mg daily intake of xanthines, continuing to within 7 days of the administration of study drug;
5. Fever (body temperature ≥38°C) or symptomatic viral or bacterial infection or febrile illness within 2 weeks prior to Screening;
6. History of recurrent (more than three episodes in 12 months) or chronic infections of any type, such as tuberculosis, sinusitis, or urinary tract infection, that in the opinion of the Investigator poses a risk to participate in the study, or any infection requiring parenteral antibiotics within the six months prior to Screening;
7. 12-lead ECG demonstrating QT interval corrected for heart rate using Fridericia's formula (QTcF) > 480 msec at the Screening Visit or history/evidence of long QT syndrome;
8. Other abnormal ECG findings at Screening that are considered by the investigator to be clinically significant;
9. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and/or total bilirubin > 1.5 × upper limit of normal at screening (elevated bilirubin acceptable if participant was known to have Gilbert's syndrome). Repeat testing at Screening is acceptable for out-of-range values following approval by the Investigator or delegate;
10. Estimated glomerular filtration rate by CKD-EPI <60 mL/min/1.73 m2
11. Pregnant or breast-feeding, or intending to become pregnant, initiate breast-feeding or donate eggs from Screening until 60 days after the last dose of study drug;
12. Positive serology test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening;
13. Positive urine toxicology screening panel or alcohol breath test;
14. History of substance abuse or dependency or history of recreational intravenous drug use over the last 5 years (by self-declaration);
15. Regular alcohol consumption within the 6 months prior to study drug administration, defined as >14 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine);
16. Use of any investigational product within the longer of 28 days or 5 half-lives prior to administration of study drug or participation in more than four investigational drug studies within 1 year prior to Screening;

17. Use of any prescription drugs, over-the-counter (OTC) (non-prescription) medication, herbal remedies (including St John's Wort), supplements or vitamins 14 days prior to dosing and during the course of study without prior approval of the Investigator and Sponsor.

    Simple analgesia (e.g., paracetamol or OTC nonsteroidal anti-inflammatory drugs) are permitted in limited doses;

18. Use of strong or moderate inhibitors or inducers of Cytochrome P450 (CYP) 3A, inhibitors or inducers of P-glycoprotein (P-gp), or drugs known to prolong the QT interval during the longer of 14 days or five half-lives prior to enrollment and during the course of the study;
19. Unwilling or unable to comply with the lifestyle guidelines outlined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteer	Drug: ZN-d5; Oral agent; 25 mg formulation; Other Names: Study Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ZN-d5 Bioavailability	Maximum concentration (Cmax)	2 months
ZN-d5 Bioavailability	Area under the plasma concentration-time curve (AUC)	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of ZN-d5	The incidence, frequency and severity of treatment-emergent adverse events (TEAEs)	2 Months
Safety and Tolerability of ZN-d5	time to maximum concentration	2 months
Safety and Tolerability of ZN-d5	delay in achieving Tmax (tlag)	2 Months
Safety and Tolerability of ZN-d5	Half-life (t1/2)	2 Months
Safety and Tolerability of ZN-d5	Volume of distribution (Vs/F)	2 months
Safety and Tolerability of ZN-d5	Clearance (CL/F)	2 months

Collaborators and Investigators

• Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
• Investigators: Study Director: Anthony Fiorino, MD, PhD, K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 4, 2021
• Primary Completion (Anticipated): July 17, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: ZN-d5-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No