cadisegliatin (TTP399) / vTv Therapeutics - LARVOL DELTA

CATT1: Cadisegliatin as Adjunctive Therapy to Insulin in Participants With Type 1 Diabetes (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: vTv Therapeutics | Suspended ➔ Recruiting | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2025 ➔ Sep 2026

Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

vTv Therapeutics Announces 2024 Fourth Quarter and Full Year Financial Results and Provides Corporate Update (GlobeNewswire) - "We expect to resume our Phase 3 CATT1 trial in patients with T1D in the second quarter of 2025 following submission of a protocol amendment shortening the trial duration from 12 to 6 months...Research & Development (R&D) Expenses: R&D expenses were $2.2 million and $2.1 million in each of the three months ended December 31, 2024, and 2023, respectively. The increase is attributable to (i) higher indirect costs of $0.7 million, partially offset by (ii) lower spending on cadisegliatin and other projects of $0.6 million..."

Commercial • Trial status • Type 1 Diabetes Mellitus

vTv Therapeutics Announces FDA has Lifted Clinical Hold on Cadisegliatin Program for Diabetes (GlobeNewswire) - "vTv Therapeutics Inc...announced that the United States Food and Drug Administration (FDA) has lifted the clinical hold on the cadisegliatin clinical program, which includes the CATT1 Phase 3 trial in type 1 diabetes (T1D)....vTv Therapeutics expects to resume the trial following submission of a protocol amendment to reduce the overall duration of the CATT1 trial from 12 months to 6 months, which will help to expedite the initiation of required larger pivotal studies for future New Drug Application (NDA) submission. The original primary endpoint of ascertaining level 2 and 3 hypoglycemia rates at 6 months will not change. The planned amendment will not include the additional 6-month period to collect safety data. By shortening the trial from 12 to 6 months, the Company will be able to obtain topline data from the study more quickly."

FDA event • Type 1 Diabetes Mellitus

Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the Traditional Chinese Medicine: In silico analysis. (PubMed, Microb Pathog) - "However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes."

Journal • Diabetes • Gestational Diabetes • Metabolic Disorders

CATT1: Cadisegliatin as Adjunctive Therapy in Type 1 Diabetes (clinicaltrials.gov) - P3 | N=150 | Suspended | Sponsor: vTv Therapeutics | Recruiting ➔ Suspended

Trial suspension • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • CRP

vTv Therapeutics Announces Cadisegliatin Program for Type 1 Diabetes Placed on Clinical Hold (GlobeNewswire) - "vTv Therapeutics...announced that the United States Food and Drug Administration (FDA) has placed a clinical hold on the cadisegliatin clinical program which includes the ongoing CATT1 Phase 3 trial in type 1 diabetes....The clinical hold was based on the discovery of a chromatographic signal in a recent human absorption, distribution, metabolism, and excretion (ADME) study of cadisegliatin that could not be resolved by standard mass spectroscopy. The Agency requires a single in vitro study to characterize this signal before the cadisegliatin program can resume."

Trial suspension • Type 1 Diabetes Mellitus

CATT1: Cadisegliatin as Adjunctive Therapy in Type 1 Diabetes (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: vTv Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • CRP

vTv Therapeutics Announces Screening of First Patient in CATT1 Pivotal Trial Evaluating Cadisegliatin for Type 1 Diabetes (GlobeNewswire) - "vTv Therapeutics...announced that the first patient has been screened in the Company’s CATT1 pivotal trial evaluating cadisegliatin as an adjunct treatment of type 1 diabetes (T1D)....CATT1 is a randomized, double-blind, placebo-controlled pivotal study evaluating the efficacy and safety of cadisegliatin over 12 months in adults 18 years or older diagnosed with T1D. The trial is expected to enroll approximately 150 patients at up to 20 sites in the U.S....Cadisegliatin will also be evaluated as an adjunctive therapy to insulin in patients with T2D as part of a planned Phase 2 trial in Middle Eastern countries in collaboration with G42 Healthcare Research Technology Projects LLC and its clinical research organization IROS, a UAE-based health technology group which is expected to start in the second half of 2024."

New P2 trial • Trial status • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

CATT1: Cadisegliatin as Adjunctive Therapy in Type 1 Diabetes (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: vTv Therapeutics

New P3 trial • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • CRP

New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment. (PubMed, Int J Mol Sci) - "Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA, TTP399, emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published preclinical studies and recent clinical trials."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The Hepatoselective Glucokinase Activator (GKA) TTP399 Does Not Increase Risk of Ketoacidosis in Type 1 Diabetes (T1D) (ADA 2022) - "Serum bicarbonate was numerically higher and urine acetoacetate was qualitatively lower in TTP399-treated subjects (Figure 1A). No patients on TTP399 met prespecified criteria for DKA while 43% of subjects on placebo did (Figure 1B, p = 0.03).These data suggest that TTP399 treatment improves glucose control with no increased risk of DKA."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators. (PubMed, J Diabetes Metab Disord) - "Although after enduring many setbacks in the development of the GK activators, interest has been renewed especially due to introduction of novel dual acting GK activator dorzagliatin, and a novel hepato-selective GK activator, TTP399. This review article has been formulated to discuss importance of GK in glucose homeostasis, recent updates on small molecules of GK activators, clinical status of GK activators and challenges in development of GK activators."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes. (PubMed, Diabetes Obes Metab) - "When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

A Comprehensive Review on Glucokinase Activators: Promising Agents for the Treatment of Type-2 Diabetes. (PubMed, Chem Biol Drug Des) - "Dorzagliatin, a novel glucokinase activator that acts on both the liver and pancreas is in the late-stage clinical development. TTP399, a promising hepatoselective GK activator showed a clinically significant and sustained reduction in glycated hemoglobin with a low risk of adverse effects. The successful findings generated immense interest to continue further research in finding small molecule GK activators for the treatment of type-2 diabetes. The article covers different series of GK activators reported over the past decade and the structural insights into the GK-GK activator binding which, we believe will stimulate the discovery of novel GK activators to treat Type-2 diabetes."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes. (PubMed, Diabetes Care) - "TTP399 lowers HbA and reduces hypoglycemia without increasing the risk of ketosis and should be further evaluated as an adjunctive therapy for the treatment of type 1 diabetes."

Clinical • Journal • P1/2 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

[VIRTUAL] Mechanism matter: preliminary evidence that activation of glucokinase by TTP399 does not increase plasma or urine ketones in type 1 diabetes (EASD 2020) - P1/2 | "These results, support the hypothesis that activation of GK by TTP399 should not increase the risk of DKA and are consistent with results from a non-clinical minipig model of T1D in which dosing of a liver-selective GKA, while reducing/eliminating insulin, did not increase ketones and protected from DKA. Further mechanistic studies and studies of longer duration are needed to confirm these observations. Clinical Trial Registration Number NCT03335371"

Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

[VIRTUAL] The Simplici-T1 trial: activation of glucokinase by TTP399 improves glycaemic control in patients with type 1 diabetes (EASD 2020) - P1/2 | "These data suggest that further development of TTP399 as adjunctive therapy in T1D is warranted. Clinical Trial Registration Number NCT03335371"

Clinical • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

"I stick with $VTVT's TTP399 for mild Alzheimers with T2D difference between night & day with Safety & Effectiveness far more Superior." (@Wows333)

Clinical • Alzheimer's Disease • CNS Disorders

[VIRTUAL] The Simplici-T1 Trial: Relationship between Glycemic Control and Insulin Dose (ADA 2020) - P1/2 | "These improvements occurred without increasing ketones in plasma or hypoglycemic events. During the 12-week treatment period, 12% of the TTP399 group and 31%of the PBO increased their insulin dose."

Late-breaking abstract • Metabolic Disorders • Type 1 Diabetes Mellitus

[VIRTUAL] The Simplici-T1 Trial: Glucokinase Activator TTP399 Improves Glycemic Control in Patients with Type 1 Diabetes (ADA 2020) - P1/2 | "Treatment-emergent adverse events were numerically lower with TTP399. No safety signals were identified.These data suggest that further development of TTP399 as adjunctive therapy in T1D is warranted."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

A 6 week pharmacokinetics, pharmacodynamics, safety and tolerability of GK1-399 in type 2 diabetes (clinicaltrials.gov) - P1/2; N=240; Suspended -> Recruiting

Enrollment open • Diabetes

Glucokinase Activators for Type 2 Diabetes: Challenges and Future Developments. (PubMed, Drugs) - "Increased hepatic glucose output, the primary liver dysregulation associated with Type 2 diabetes mellitus (T2DM), is not directly or effectively targeted by the currently available classes of glucose-lowering medications except metformin. Despite several setbacks in their development, interest in the GKA class has been renewed, particularly since the introduction of a novel, dual-acting full GKA, dorzagliatin, and a novel hepatoselective molecule, TTP399. In this article we provide an overview of the role, efficacy, safety and future developments of GKAs in the management of T2DM."

Journal

Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator. (PubMed, Sci Transl Med) - "Compared to placebo, TTP399 (800 mg/day) also increased high-density lipoprotein cholesterol (3.2 mg/dl; P < 0.05), decreased fasting plasma glucagon (-20 pg/ml; P < 0.05), and decreased weight in patients weighing ≥100 kg (-3.4 kg; P < 0.05). TTP399 did not cause hypoglycemia, had no detrimental effect on plasma lipids or liver enzymes, and did not increase blood pressure, highlighting the importance of tissue selectivity and preservation of physiological regulation when targeting key metabolic regulators such as GK."

Journal

SimpliciT1: Evaluation of TTP399 in Patients With Type 1 Diabetes (clinicaltrials.gov) - P1/2; N=115; Completed; Sponsor: vTv Therapeutics; Active, not recruiting ➔ Completed

Trial completion

vTv Therapeutics: Announces completion of Phase 1b study evaluating TTP399 for the treatment of type 1 diabetes (Market Screener) - "'There is a tremendous need for new, safe and effective treatment options for the millions of people living with T1D,' said Dr. John Buse...principal investigator for this study. 'Maintaining glucose control is imperative for those with T1D and we are optimistic that treatment with TTP399 could potentially offer an improved therapy.'"

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