Phase 1/1b Study of TLC-6740 in Healthy Subjects and Subjects With Obesity, With or Without Diabetes

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorOrsoBio, Inc

About this trial

The phase 1 portion of the study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-6740 after single- and multiple-ascending doses in healthy subjects. The phase 1b portion of the study is designed to assess the safety, tolerability, and PK of TLC-6740 in subjects with obesity, with or without type 2 diabetes mellitus.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Non-smoking, healthy male or female subject between 18 and 55 years of age, inclusive (Parts A-E); male or female subject between 18 and 70 years of age, inclusive (Parts F, G)

Body mass index (BMI) from 19 to 35 kg/m2, inclusive (Parts A-E); BMI ≥ 30 kg/m2 and ≤ 50 kg/m2 (Parts F, G)

Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min (Parts A-E); eGFR ≥ 60 mL/min/1.73m2 or eGFR ≥ 45 mL/min/1.73m2, depending on cohort (Parts F, G)

ALT/AST/ALP ≤ 1 x ULN (Parts A-E); ALT/AST < 3 x ULN, ALP < 1.5 x ULN (Parts F, G)

Disqualifiers

Pregnant or lactating subjects

Unstable type 2 diabetes (as defined as: HbA1c > 10.0%; treatment with insulin and/or pioglitazone within 90 days prior to Screening; any history of diabetic ketoacidosis, hyperosmolar state, and/or acutely decompensated blood glucose control; hypoglycemia unawareness, hospitalization due to hypoglycemia, or history of severe hypoglycemia [requiring outside assistance to regain normal neurologic status]) (Part F)

History of type 2 diabetes diagnosed prior

Medical history of type 1 diabetes or latent autoimmune diabetes of adults (LADA)

Trial design

Design model

Sequential

Treatments tested in this trial

  • TLC-6740 Oral Solution

    Drug

    Oral solution of TLC-6740

  • Placebo Oral Solution

    Other intervention

    Placebo-to-match oral solution TLC-6740

  • TLC-6740 Tablet

    Drug

    Tablet formulation of TLC-6740

  • Drug Metabolizing Enzyme

    Drug

    Oral dose of omeprazole, voriconazole, itraconazole, or rifampicin

  • Tirzepatide

    Drug

    Subcutaneous injection of tirzepatide

  • Placebo Tablet

    Other intervention

    Placebo-to-match tablet formulation of TLC-6740

Treatment groups

564 Participants
are divided into 5 treatment groups
Group A: Oral SolutionExperimental treatment 2 interventions
Group B: TabletExperimental treatment 2 interventions
Group C: Drug Metabolizing EnzymeExperimental treatment 2 interventions
Group D: TLC-6740 + TirzepatideExperimental treatment 2 interventions
Group E: Placebo + TirzepatideExperimental treatment 0 interventions

Trial outcomes

Primary outcomes

1

Incidence of TLC-6740 treatment-emergent adverse events

Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related.

Time frame
Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
2

PK of TLC-6740 AUC

Area under the concentration-time curve

Time frame
Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
3

PK of TLC-6740 Cmax

Maximum plasma concentration

Time frame
Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study
4

PK of TLC-6740 tmax

Time to reach Cmax

Time frame
Through study completion: up to Day 15 (Parts A, C); Day 24 (Parts B, C); Day 22 (Part D); Day 49 (Part E); Day 168 (Parts F, G) of the study

Secondary outcomes

Other outcomes

Sponsors and contacts

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