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Trial record 1 of 1 for:    LBS-008
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Safety and Tolerability Study of LBS-008 in Healthy Adult Subjects After Single and Multiple Doses

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ClinicalTrials.gov Identifier: NCT03735810
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : June 18, 2019
Sponsor:
Collaborator:
Belite Bio, Inc
Information provided by (Responsible Party):
RBP4 Pty Ltd

Brief Summary:

A double-blind, placebo-controlled, single ascending dose (SAD) study is planned to assess safety, pharmacokinetics (PK), and pharmacodynamics of LBS-008 in healthy adult volunteers. Healthy male or female adults with no significant ocular abnormalities will be enrolled. The plan is to enroll 40 subjects, in five cohorts of eight subjects each; additional cohorts (eight subjects per cohort) may be enrolled if it is deemed appropriate by the sponsor to repeat a dose level or to study another dose level. Within each cohort, six subjects will be randomized to receive active drug and two subjects will receive placebo. Each subject will participate in only one dose level. Subjects will receive single ascending doses of 50, 100, 200, 400, and 25 mg LBS-008 administered as 25 or 200 mg capsules, or an equivalent number of placebo capsules. Each dose cohort will be separated into two groups; a sentinel group of two subjects (one active and one placebo) will be dosed at least 24 hours before the remaining six subjects (five active and one placebo).

The MAD portion will start after the completion of Cohort 4 of SAD and will have up to 4 cohorts and up to a total of 32 subjects (8 subjects per cohort). The starting dose of LBS-008 will be 10 mg and the planned doses for subsequent cohorts are 25, 50 and 100 mg. The final doses are determined based on the outcome of SAD portion.


Condition or disease Intervention/treatment Phase
Healthy Volunteer Drug: LBS-008 Drug: Placebos Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LBS-008 in Healthy Adult Subjects
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : November 2019

Arm Intervention/treatment
Experimental: Single Ascending Dose (SAD)
The SAD portion will undergo screening visit and 1 day for follow-up. Healthy volunteers will be enrolled in 5 dose cohorts(8 subjects per cohorts), starting at 50 milligram [mg], 100, 200, 400, and 25 mg, and will receive single oral dose of LBS-008 at Day 1.
Drug: LBS-008
LBS-008

Experimental: Multiple Ascending Dose (MAD)
The MAD portion will start after the completion of Cohort 4 of SAD. There are 4 cohorts (8 subjects per cohort) and starting dosing of LBS-008 will be 10 mg, 25, 50 and 100 mg for subsequent cohorts. All subjects will receive LBS-008 orally for 14 days.
Drug: LBS-008
LBS-008

Placebo Comparator: Placebo

Healthy volunteers will receive the placebo capsules matching as LBS-008 capsules.

There are 2 subjects per cohorts of SAD and MAD.

Drug: Placebos
Placebo




Primary Outcome Measures :
  1. PK analysis: Area under the plasma concentration versus time curve from time 0 to the last timepoint with quantifiable concentration (AUC0-t) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  2. PK analysis: Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  3. PK analysis: Maximum observed plasma concentration (Cmax) [ Time Frame: SAD portion: Day 1 to Day 6; MAD portion: Day 1 to Day 28 ]
  4. PK analysis: Time to maximum observed plasma concentration (Tmax) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 17 ]
  5. PK analysis: Terminal elimination rate constant [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  6. PK analysis: Terminal phase half-life (t1/2) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  7. PK analysis: Apparent total body clearance (CL/F) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  8. PK analysis: Apparent volume of distribution (Vz/F) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  9. PK analysis: Accumulation ratio for Cmax (MAD Cohort 1 thru 4). RCmax = Cmax,Day14 / Cmax,Day 1 [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  10. PK analysis: Accumulation ratio for AUC (MAD Cohort 1 thru 4). RAUC24 = AUC0-24,Day14 / AUC0-24,Day1 [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]

Secondary Outcome Measures :
  1. Plasma concentrations of RBP4: Time to minimal RPB4 levels postdose (Tmin) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  2. Maximal suppression to RBP4 expressed as minimum concentration of RBP4 (Cmin) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  3. Maximal suppression to RBP4 expressed as percent (%) of baseline concentration of RBP4 (C%bmin) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  4. RBP4 level at 12 hours as concentration (C12h) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  5. RBP4 level at 12 hours as percent (%) of baseline concentration (C%b12h) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  6. RBP4 level at 24 hours as concentration (C24h) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  7. RBP4 level at 24 hours as percent (%) of baseline concentration (C%b24h) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]
  8. Half-life for recovery of RBP4 to baseline levels (PDt1/2) [ Time Frame: SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. The subject is male or female, 18 to 65 years of age, inclusive, at screening.
  2. The subject voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures.
  3. The subject is willing and able to remain in the study unit for the entire duration of the confinement period and return for outpatient visits.
  4. Female subjects must be of nonchildbearing potential (defined as surgically sterile [i.e., had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months before the dose of study drug] or postmenopausal for at least 1 year before study drug administration confirmed by FSH test at screening; FSH level >40 mIU/mL). Female subjects may also be considered of non-childbearing if they have a confirmed medical condition which would deem the subject as infertile. E.g. MRKH Syndrome (Mullerian Agenesis) or another applicable condition.
  5. Male subjects must be surgically sterile (i.e., vasectomy) for at least 3 months before screening; or remain abstinent or agree to use a highly effective form of contraception when sexually active with a female partner for 90 days after study drug administration. Highly effective contraception requires use of a condom and appropriate contraceptive measures for your female partner (i.e. oral, injected or implanted hormonal methods, or placement of an intrauterine device or intrauterine system). This requirement does not apply to subjects in a same sex relationship and female partners of non-childbearing potential.
  6. The subject has a body mass index (BMI) of 18 to 30 kg/m2, inclusive, and weighs 50 to 100 kg (110 to 220 pounds), inclusive, at screening and check-in.
  7. The subject is considered to be in stable health by the investigator, as determined by:

    • Ophthalmic history with no clinically significant abnormalities
    • Pre-study ocular exam with no clinically significant abnormalities
    • Pre-study best corrected visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) (Method 2)
    • Normal D-15 Dichotomous Hue color vision testing (tested monocularly, with Total Error Score within normal limits)
    • Vital signs at screening and Check-in within normal ranges or if outside of the normal ranges are not deemed clinically significant in the opinion of the investigator
    • Liver function tests (aspartate transaminase, alanine transaminase, bilirubin, and alkaline phosphatase) within 1.5 x the upper limit of normal (ULN)
    • All other pre-study clinical laboratory findings within normal range, or if outside of the normal range are not deemed clinically significant in the opinion of the investigator
    • 12-Lead electrocardiogram (ECG) showing no clinically significant abnormalities
  8. The subject agrees to comply with all protocol requirements.

Exclusion Criteria:

  1. The subject has a history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
  2. The subject has vitamin A deficiency as defined based upon serum values less than 20 mcg/dL (=0.7 µmol/L) or clinical signs during slit-lamp examination (conjunctival or corneal xerosis; Bitot's spots; corneal ulcers or scarring not due to trauma or other secondary causes).
  3. The subject has had a clinically significant new illness within 1 month before screening.
  4. The subject has had symptoms or illness compatible with gastrointestinal or respiratory viral syndrome within 2 weeks before screening.
  5. The subject has had previous or current participation in any clinical study with an investigational drug, biologic, or device with a last dose within 6 weeks before the screening visit.
  6. The subject has a history of severe drug or excipient allergy or hypersensitivity.
  7. The subject has donated or lost in excess of 500 mL of blood within 56 days of study treatment administration.
  8. The subject has donated plasma within 7 days before study treatment administration.
  9. The subject has a recent history (within 2 years before the screening visit) of alcohol or drug/solvent abuse or a positive screen for alcohol or drugs of abuse, including marijuana, at screening and Check-in.
  10. The subject has a history of retinal macular edema or other retinal disorders.
  11. The subject has a history of treatment with retinal toxic medications, such as chloroquine, hydroxychloroquine, vigabatrin, isotretinoin, tamoxifen, thioridazine.
  12. The subject has a history of or positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.
  13. The subject has a history of hypertension, coronary artery disease, or any other significant cardiovascular disease.
  14. The subject has a history of diabetes.
  15. The subject has a systolic blood pressure of <90 mmHg or >140 mmHg, or a diastolic blood pressure <50 mmHg or >90 at screening, on Day -1, or predose.
  16. The average of triplicate safety ECGs for male subjects is a QT interval corrected using Fridericia's formula (QTcF) of >450 msec, or for female subjects with a QTcF >470 msec at screening.
  17. The subject has a history of unexplained loss of consciousness, epilepsy or other seizure disorder, or cerebrovascular disease.
  18. The subject has had a malignancy within 5 years of the screening visit (with the exception of basal cell and squamous cell skin carcinoma).
  19. The subject has been on a significantly abnormal diet, in the opinion of the investigator, during the 4 weeks preceding study treatment administration.
  20. The subject has used any over-the-counter medication (including nutritional or dietary supplements, herbal preparations, or vitamins) with the exception of occasional paracetamol use (up to 2g per day) within 7 days before study treatment administration.
  21. The subject has used any prescription medication, except hormonal replacement therapy, within 7 days before study treatment administration.
  22. The subject has used any kind of prescription or non-prescription oral or topical retinoids (for "aging") within 2 weeks before study treatment administration.
  23. The subject has been treated with any known drugs or supplements that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes (e.g., rifampin, barbiturates, phenothiazines, cimetidine, carbamazepine, St. John's wort) within 30 days before the dose of study drug, and that, in the investigator's judgment, may impact subject safety or the validity of the study results.
  24. The subject has engaged in strenuous exercise, as judged by the investigator, from 48 hours before the dose of study drug.
  25. The subject has consumed beverages or foods that contain alcohol, grapefruit, poppy seeds, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine within 48 hours before the dose of study drug.
  26. The subject has consumed more than 2 cups of coffee or 2 soda cans per day between 1 to 6 prior to check-in.
  27. The subject has smoked or used tobacco- or nicotine-containing products within 28 days prior to the dose of study drug or has a positive test result for cotinine at screening and Day -1.
  28. In the opinion of the investigator, the subject is not suitable for entry into the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03735810


Contacts
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Contact: Lara Hatchuel 0424686547 lhatchuel@linear.org.au

Locations
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Australia
Linear Clinical Research Recruiting
Perth, Australia, 6009
Contact: Lara Hatchuel, MD         
Sponsors and Collaborators
RBP4 Pty Ltd
Belite Bio, Inc

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Responsible Party: RBP4 Pty Ltd
ClinicalTrials.gov Identifier: NCT03735810     History of Changes
Other Study ID Numbers: LBS-008-CT01
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD will not be available

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes