crisugabalin (HSK16149) / Haisco - LARVOL DELTA

New Tricyclic γ‑Aminobutyric Acid Analogue HSK16149: A Ca2+ Channel α2‑δ Ligand for Treating Neuropathic Pain. (PubMed, ACS Med Chem Lett) - "Pregabalin and gabapentin are currently first-line treatments for neuropathic pain, but common adverse effects such as dizziness and somnolence frequently lead to treatment discontinuation. HSK16149 also demonstrated superior antihypersensitivity or antiallodynic/hyperalgesic effects compared to the commonly used pregabalin as the control and has the potential to minimize CNS side effects with good tolerability. Based on its exceptional preclinical characteristics, HSK16149 was chosen for further development to provide a more effective and safer drug for patients enduring neuropathic pain."

Journal • Immunology • Neuralgia • Pain

The Efficacy and Safety of Pregabalin and Crisugabalin in Patients With Fibromyalgia (clinicaltrials.gov) - P=N/A | N=362 | Recruiting | Sponsor: Beijing Tiantan Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Evaluation of the Efficacy and Safety of Crisugabalin Capsules versus Placebo and Venlafaxine Extended-Release (XR) Capsules in Chinese Patients with Generalized Anxiety Disorder: A Prospective, Multicenter, Randomized, Double-Blind, Double-Dummy, Active- and Placebo-Controlled Clinical Trial (CEASE-GAD). (ChiCTR) - P4 | N=216 | Not yet recruiting | Sponsor: The first affiliated hospital of anhui medical university; The first affiliated hospital of anhui medical university

New P4 trial • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment. (PubMed, Br J Clin Pharmacol) - "For patients with GFR < 60 mL/min, dosage adjustments of crisugabalin should be considered. To maintain comparable plasma drug concentrations in patients with impaired renal function, it is recommended that crisugabalin doses be decreased by approximately 50% for every 50% decline in GFR."

Journal • PK/PD data • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain • Renal Disease

The Efficacy and Safety of Pregabalin and Crisugabalin in Patients With Fibromyalgia (clinicaltrials.gov) - P=N/A | N=362 | Not yet recruiting | Sponsor: Beijing Tiantan Hospital

Monotherapy • New trial • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

To Evaluate the Long-term Safety and Efficacy of HSK16149 in Chinese Patients With Peripheral Neuralgia (clinicaltrials.gov) - P3 | N=301 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Neuralgia • Pain • Peripheral Neuropathic Pain

Efficacy and Safety of Crisugabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain and Inadequate Response to Pregabalin—A Phase 2 Randomized Clinical Trial (ADA 2025) - "In Chinese patients with DPNP who had an inadequate response to Pregabalin, Crisugabalin was superior to Pregabalin in reducing DPNP symptoms and was well tolerated."

Clinical • P2 data • Diabetic Neuropathy • Metabolic Disorders

An Observational Cohort Study of Early Response to Therapy and Safety of Crisugabalin Besilate Capsules for the Treatment of Neuropathic Pain in the Real World (ChiCTR) - P4 | N=1000 | Not yet recruiting | Sponsor: The first affiliated hostipal of nanchang university; The first affiliated hostipal of nanchang university

New P4 trial • Real-world evidence • Neuralgia • Pain

An observational cohort study of the efficacy and safety of crisugabalin besilate capsules for the treatment of patients with acute herpes zoster in the real world (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: Hangzhou Third People's Hospital; Hangzhou Third People's Hospital

New trial • Real-world evidence • Herpes Zoster • Varicella Zoster

CRYSTAL: Crisugabalin for Radiotherapy-Related Neuropathic Pain (clinicaltrials.gov) - P2 | N=172 | Recruiting | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2025 ➔ May 2025

Enrollment open • Head-to-Head • Trial initiation date • Head and Neck Cancer • Neuralgia • Oncology • Pain • Solid Tumor

Rapid Onset of Pain Relief with Crisugabalin in Patients with Diabetic Peripheral Neuropathic Pain: Findings from a Multicenter, Randomized, Double-Blind, Controlled Study. (PubMed, Pain Ther) - P2/3 | "The findings suggest that Crisugabalin offers effective pain relief with an acceptable safety profile, highlighting its rapid onset in patients with DPNP."

Clinical • Journal • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Crisugabalin, a ligand for the α2δ subunit of voltage-gated calcium channels, exhibits no obvious abuse potential in rodents. (PubMed, Pharmacol Biochem Behav) - "Secondly, a rat drug discrimination study was employed to determine the pharmacological similarity between crisugabalin and the training drug midazolam. In the rat spontaneous withdrawal study, crisugabalin demonstrated a very low level of physical dependence. These findings suggest that crisugabalin has minimal to no potential for abuse, thereby establishing itself as a safer option relative to pregabalin and mirogabalin."

Journal • Preclinical • CNS Disorders • Diabetic Neuropathy • Epilepsy • Neuralgia • Pain • Peripheral Neuropathic Pain

CRYSTAL: Crisugabalin for Radiotherapy-Related Neuropathic Pain (clinicaltrials.gov) - P2 | N=172 | Not yet recruiting | Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

New P2 trial • Head and Neck Cancer • Neuralgia • Oncology • Pain • Solid Tumor

Quantification of crisugabalin (HSK16149) in biological matrix by LC-MS/MS method: An application to rat pharmacokinetic and tissue distribution studies. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "In rats, orally administered crisugabalin was completely and rapidly absorbed with a peak time of about 0.57 h, and was mainly distributed to kidney, bladder and liver tissues. Crisugabalin exhibited linear pharmacokinetics over the oral dose range of 3-30 mg/kg."

Journal • PK/PD data • Preclinical • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial. (PubMed, JAMA Dermatol) - P3 | "Participants included adults with postherpetic neuralgia with an average daily pain score (ADPS) of at least 4 on the 11-point Numeric Pain Rating Scale over the preceding week, with the exclusion of patients with pain not controlled by prior therapy with pregabalin (≥300 mg/d) or gabapentin (≥1200 mg/d). Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo. ClinicalTrials.gov Identifier: NCT05140863."

Clinical • Journal • P3 data • Neuralgia • Pain

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2/3 | "This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. ClinicalTrials.gov Identifier: NCT04647773."

Clinical • Journal • P3 data • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Diabetic Peripheral Neuropathic Pain Who Had an Inadequate Response to Pregabalin (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P2 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Long-Term Efficacy and Safety of Crisugabalin Besilate in Chinese patients with Diabetic Peripheral Neuropathic Pain (ADA 2024) - "Long-term treatment with Crisugabalin Besilate is effective and safe for pain relief in Chinese patients with DPNP."

Clinical • Diabetic Neuropathy • Metabolic Disorders

Efficacy and Safety of Crisugabalin with Acetyl-Levo-Carnitine in Chinese Patients with Diabetic Peripheral Neuropathic Pain—A Multicentre, Randomized, Open-Label, Positive-Controlled, Parallel-Group, Phase 2 Trial (ADA 2024) - "These preliminary data demonstrated that Crisugabalin with ALC was superiority to LA with ALC in relieving pain and well tolerated in Chinese patients with DPNP."

Clinical • P2 data • Diabetic Neuropathy • Metabolic Disorders

Efficacy and Safety of HSK16149 Capsule in the Treatment of Moderate and Severe Central Neuropathic Pain in China (clinicaltrials.gov) - P3 | N=408 | Not yet recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P3 trial • Central Neuropathic Pain • Neuralgia • Pain

A phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel, potent GABA analog HSK16149 in healthy Chinese subjects. (PubMed, Front Pharmacol) - "Based on the safety and pharmacokinetic data, 80 mg twice daily (BID) was suggested as the highest target dose for further clinical development. Clinical Trial Registration: http://www.chinadrugtrials.org.cn, identifier CTR20182535 and CTR20191317."

Clinical • Journal • P1 data • PK/PD data • Neuralgia • Pain

The Drug-drug Interaction of HSK16149 Capsule With Probenecid Tablets or Cimetidine Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed

Trial completion

To Evaluate the Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Herpetic Neuralgia (clinicaltrials.gov) - P2 | N=331 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed

Trial completion • Neuralgia • Pain

To Evaluate the Efficacy and Safety of HSK16149 With L-carnitine in Diabetic Peripheral Neuralgia Patients in China (clinicaltrials.gov) - P=N/A | N=136 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Haisike: Obtained the "Acceptance Notice" for the new indication marketing application of innovative drug HSK16149 capsules (Daily Economic News - NBD) - "Haisike announced that it has received the 'Acceptance Notice' for the new indication marketing application of the innovative drug HSK16149 capsules. The indication is post-herpetic neuralgia."

Non-US regulatory • Neuralgia • Pain • Peripheral Neuropathic Pain