A Study of the Safety and Tolerability of CDX-6114 in Healthy Volunteers

NCT ID: NCT03797664

Last Updated: 2021-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-14
• Study Completion Date: 2019-04-12

Brief Summary

The purpose of this study is to assess the safety and tolerability of an oral solution of CDX-6114 when administered as a single dose in healthy volunteers

Detailed Description

This is a second Phase 1, double-blind, placebo-controlled study in approximately 24 healthy volunteers who are 18 to 55 years old. Three cohorts are planned each consisting of 8 subjects; the cohorts as planned are 7.5, 15.0 and 22.5 g of CDX-6114 (or matching placebo) in oral solution. Increasing doses of CDX-6114 will be assessed sequentially un til the final dose is evaluated or any of the stopping criteria are reached. Subjects will each receive either a single dose of CDX-6114 or matching placebo, with food, and will then be followed for a total of 22 days (3 weeks).

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental: CDX-6114

7.5, 15.0 and 22.5g

Group Type: EXPERIMENTAL

CDX-6114

Intervention Type: DRUG

CDX-6114 will be administered as a single, oral dose solution at dose levels of 7.5, 15.0 and 22.5g

Placebo Comparator: Placebo

Phosphate Buffer Diluent Solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Phosphate Buffer Diluent oral solution

Interventions

CDX-6114

CDX-6114 will be administered as a single, oral dose solution at dose levels of 7.5, 15.0 and 22.5g

Intervention Type: DRUG

Placebo

Phosphate Buffer Diluent oral solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Healthy male and female, non-smoking, subjects between the ages of 18 and 55 years, inclusive, at the time of screening.

2. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

3. Good general health, as determined by an experienced physician based on a medical evaluation including detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead electrocardiogram (ECG) and clinical laboratory tests.

4. Male subjects and their female spouse/partner(s) who are of childbearing potential:

1. Must agree to stay abstinent (where abstinence is the preferred and usual life-style of the subject), starting at screening and continuing throughout the clinical study period, and for 90 days after study drug administration.

Or

2. Must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the clinical study period, and for 90 days after study drug administration.

3. These requirements do not apply to participants in a same sex relationship.

5. Male subjects must agree not to donate sperm starting at screening and continuing throughout the clinical study period, and for 90 days after study drug administration.

6. Female subjects of childbearing potential:

1. Must agree not to become pregnant during the clinical study period and for 30 days after study drug administration.

2. Must have a negative serum pregnancy test at screening.

3. If heterosexually active, must agree to consistently use a form of highly effective birth control, in combination with a barrier method starting at screening and continuing throughout the clinical study period, and for 30 days after study drug administration

Or

4. Must agree to stay abstinent, (where abstinence is the preferred and usual life-style of the subject), starting at screening and continuing throughout the clinical study period, and for 30 days after study drug administration.

5. These requirements do not apply to participants in a same sex relationship.

7. Female subjects of non-childbearing potential:

1. Must have a confirmed clinical history of sterility

Or

2. Must be postmenopausal as defined as: amenorrhea for at least 1 year prior to screening and a laboratory confirmed serum follicle stimulating hormone (FSH) level ≥ 40mIU/mL.

8. Female subjects must agree not to breastfeed starting at screening and continuing throughout the clinical study period, and for 90 days after study drug administration.

9. Female subjects must agree not to donate ova starting at screening and continuing throughout the clinical study period, and for 90 days after study drug administration.

10. Subject must be competent to understand the nature of the study & capable of giving written informed consent. Be willing to report for the scheduled study visits and communicate to study personnel about adverse events and concomitant medication use.

11. Subject must abstain from the following foods from 1 week prior to study drug administration until the last PK sample has been obtained: grapefruit juice or products, pomegranate juice or products, foods containing poppy seeds, and/or drinks or foods containing quinine (e.g., tonic water) or Seville oranges (e.g., orange marmalade).

12. Subject agrees not to participate in another interventional study while participating in the present clinical study.

-

Exclusion Criteria

1. Female subject who has been pregnant within the 6 months prior to screening or breastfeeding within the 3 months prior to screening.

2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma) at time of study drug administration.

3. Current or chronic history of gastrointestinal illness or conditions interfering with normal gastrointestinal anatomy or motility. Examples include gastrointestinal bypass surgery, cholecystectomy, partial or total gastrectomy, gastric band surgery, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, irritable bowel syndrome (IBS) or celiac sprue.

4. Treatment with any anti-platelet and/or anticoagulant medication.

5. Evidence or history of specific food intolerance. Examples include gluten intolerance, lactose intolerance, or dairy food intolerance or any food/ingredient included in the protein breakfast.

6. A positive result, on screening, for serum hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (HAV), hepatitis C virus antibodies (HCV) or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2).

7. A positive pre-study drug/alcohol screen. However, there is the option to re-screen during the screening period at the discretion of the PI or delegate in the case of a positive pre-study drug screen for a prescribed medication e.g. codeine.

8. Subject has a history of drinking > 21 units of alcohol/week for male subjects or > 14 units of alcohol/week for female subjects within the 3 months prior to screening.

9. Subject has a history of regular smoking (daily or most days in a week) or the use of nicotine products (3 or more nicotine-containing products) within the 6 months prior to screening.

10. Subjects who show evidence of use of any recreational drugs of abuse on testing or recent history (within the 3 months prior to screening).

11. Subject has a pulse rate <40 or > 100 bpm; mean systolic blood pressure (SBP) > 140 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg at screening. Repeat measurements are allowed at the discretion of the PI or delegate.

12. Subject has any clinically significant abnormalities at screening in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the Investigator, that may interfere with the interpretation of QTc interval changes including abnormal ST-T wave morphology.

13. Subject has prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) > 450 ms for male subjects or > 470 ms for female subjects, or shortened QTcF < 300 ms or a family history of prolonged QT syndrome, at screening.

14. Subject has any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis at screening as judged by the Investigator, including: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) or Total bilirubin (TBL) more than 1.5 times the Upper Limit of Normal (ULN).

15. Plasma donation within the 14 days prior to screening or any whole blood donation/significant blood loss > 500 mL during the 3 months prior to screening.

16. Treatment with any Investigational Drug or Device/Treatment within the 30 days prior to the administration of study drug.

17. Use of any prescribed or non-prescribed medication including, herbal and dietary supplements, antacids, analgesics (other than oral contraceptives, paracetamol or multi-vitamins) during the two weeks prior to the administration of the study drug, or up to a minimum of 5 times the half-life of the medication if it has a long half-life.

18. Previous treatment with CDX-6114 active study drug (but not placebo) in study CDX6114-001.

19. Known allergy or adverse reaction history to any of the oral dose formulation components e.g. mannitol

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• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Codexis Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sam Salman

Role: PRINCIPAL_INVESTIGATOR

Linear Clinical Services

Locations

Linear Clinical Services

Perth, Western Australia, Australia

Countries

Australia

Other Identifiers

CDX6114-004

Identifier Type: -

Identifier Source: org_study_id