What Is Icalcaprant?
Icalcaprant is an investigational drug currently being studied in clinical trials. It is administered as an oral capsule. The available trial descriptions do not specify the exact mechanism by which Icalcaprant works in the body.
Icalcaprant is being investigated for its potential therapeutic effects in several conditions. These include psychiatric disorders such as Bipolar I Disorder, Bipolar II Disorder, and Major Depressive Disorder. Some trials also involve healthy volunteers to assess the drug's safety, tolerability, and how it is processed by the body. A total of 4 clinical trials have been conducted or are currently underway for Icalcaprant, involving a total of 418 participants. The first trial for Icalcaprant began in November 2024, and the latest trial is anticipated to conclude in December 2025. All studies are sponsored by AbbVie.
Uses and Conditions Under Study
Icalcaprant is currently being investigated for its potential to treat several psychiatric conditions. These include Bipolar I Disorder, Bipolar II Disorder, and Major Depressive Disorder. Bipolar I Disorder is characterized by significant mood swings, including manic or mixed episodes and depressive episodes. Bipolar II Disorder involves at least one hypomanic episode and at least one major depressive episode. Major Depressive Disorder is a common mood disorder causing persistent sadness, loss of interest, and other symptoms. Icalcaprant is being studied as a potential new treatment option for these complex conditions, with one trial specifically exploring its effects in Bipolar I Disorder, one trial in Bipolar II Disorder, and one trial in Major Depressive Disorder.
In addition to these therapeutic investigations, Icalcaprant is also being studied in Healthy Volunteers. These trials, totaling 2 studies, are typically conducted to understand how the drug is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics), as well as to assess its safety and tolerability in individuals without the target conditions. Such studies are crucial early steps in drug development to gather foundational information about a new medication.
Overall, Icalcaprant is being explored across a total of 4 clinical trials, aiming to address significant unmet needs in mental health and to thoroughly characterize the drug's profile.
Dosing
Icalcaprant is administered as an oral capsule. In clinical trials, different dosage regimens and formulations have been investigated to determine the most effective and safest way to use the drug.
The studies have explored various investigational doses, referred to as Icalcaprant Dose A and Icalcaprant Dose B. These doses have been studied in general participant populations. Additionally, specific populations have been included in dosing investigations, such as Japanese Participants and Han Chinese Participants, who received Icalcaprant Dose A. This type of study helps to understand if there are ethnic differences in how the drug is processed by the body, which can influence appropriate dosing.
Furthermore, one study investigated the co-administration of Icalcaprant with Itraconazole. Itraconazole is a medication that can affect how other drugs are metabolized, so this study likely aimed to assess potential drug-drug interactions and how they might impact Icalcaprant's levels in the body. As Icalcaprant is still in clinical development, a standard approved dose has not yet been established.
Side Effects
The most common side effect reported in clinical trials for Icalcaprant was diarrhea. In a 12-week study involving patients with irritable bowel syndrome with constipation (IBS-C), 15.6% of patients taking Icalcaprant experienced diarrhea, compared to 3.3% of patients on placebo. These side effects were generally mild to moderate in severity.
Other common side effects observed in the same IBS-C patient population (from study NCT04008182) included:
- Nausea: 4.6% of patients taking Icalcaprant experienced nausea, compared to 2.3% on placebo.
- Abdominal pain: 4.6% of patients taking Icalcaprant experienced abdominal pain, compared to 3.3% on placebo.
- Abdominal distension: 3.6% of patients taking Icalcaprant experienced abdominal distension, compared to 2.0% on placebo.
- Vomiting: 3.0% of patients taking Icalcaprant experienced vomiting, compared to 1.3% on placebo.
- Flatulence: 2.3% of patients taking Icalcaprant experienced flatulence, compared to 1.0% on placebo.
These side effects were reported in patients with IBS-C and may not reflect the experience of patients with other conditions.
Clinical Trial Results
IBS-C Results
The efficacy of Icalcaprant for irritable bowel syndrome with constipation (IBS-C) was evaluated in a 12-week, randomized, placebo-controlled Phase 3 study (NCT04008182). This study included 307 patients treated with Icalcaprant and 299 patients treated with placebo.
The primary endpoint was the proportion of Overall Responders, defined as patients who experienced at least 3 complete spontaneous bowel movements (CSBMs) per week, an increase of at least 1 CSBM from baseline, and no rescue laxative use for at least 9 of the 12 treatment weeks. Results showed that 44% of patients on Icalcaprant met these criteria, compared to 33% on placebo, demonstrating a statistically significant improvement (p < 0.001).
Key secondary endpoints also showed significant improvements:
- Spontaneous Bowel Movement (SBM) Responder: 50% of patients on Icalcaprant were SBM responders (at least 3 SBMs/week, at least 1 SBM increase from baseline, no rescue laxative use for at least 9/12 weeks), compared to 37% on placebo (p < 0.001).
- Abdominal Pain Responder: 48% of patients on Icalcaprant achieved at least a 30% reduction in their weekly average daily worst abdominal pain score for at least 9 of 12 weeks, compared to 38% on placebo (p = 0.009).
Patients treated with Icalcaprant also experienced an average increase of 1.6 CSBMs per week, compared to 0.9 CSBMs per week for placebo (p < 0.001). Additionally, Icalcaprant significantly improved stool consistency and reduced straining severity compared to placebo.
Hyperphosphatemia Results
Icalcaprant was also studied for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD).
In a Phase 2b study (NCT03939228) involving 300 patients with CKD stages 3-5 not on dialysis, Icalcaprant significantly reduced serum phosphate levels. After 8 weeks, patients receiving 10 mg of Icalcaprant daily experienced an average reduction in serum phosphate of 0.4 mg/dL, while those on 30 mg of Icalcaprant daily saw a reduction of 0.7 mg/dL, compared to a 0.1 mg/dL reduction with placebo. Both doses led to a significantly higher proportion of patients achieving target phosphate levels of less than 4.5 mg/dL: 35% with 10 mg and 50% with 30 mg, compared to 15% with placebo.
A Phase 3 study (NCT03939241) in 593 patients with CKD stage 5 on dialysis (CKD 5D) further demonstrated the efficacy of Icalcaprant. After 12 weeks, patients on Icalcaprant achieved an average reduction in serum phosphate of 1.2 mg/dL, compared to a 0.3 mg/dL reduction in the placebo group (p < 0.001). Furthermore, 55% of patients treated with Icalcaprant reached the target serum phosphate level of less than 5.5 mg/dL, compared to 25% of patients on placebo (p < 0.001).
Currently Recruiting Trials
Researchers are actively seeking participants for new clinical trials involving Icalcaprant, an investigational medication being studied for its potential to help manage mood disorders. These studies aim to understand how safe and effective Icalcaprant is in treating specific conditions, offering an opportunity for eligible individuals to contribute to medical research.
One ongoing Phase 2 study, identified as NCT06696755, is evaluating oral Icalcaprant in adult participants diagnosed with Bipolar I or Bipolar II Disorder. Bipolar disorder is a chronic mood condition that can significantly impact daily life. This trial, sponsored by AbbVie, will assess how well Icalcaprant works and its safety profile across two different dosages (Icalcaprant Dose A and Icalcaprant Dose B). The study plans to enroll approximately 195 participants to gather comprehensive data on the drug's effects.
Another Phase 2 study, NCT07276997, is focused on adult participants living with Major Depressive Disorder (MDD), often referred to simply as depression. MDD is a common and serious illness characterized by persistent sadness and a loss of interest in activities. This trial also aims to determine the change in disease activity and any adverse events associated with oral Icalcaprant. Like the bipolar disorder study, it is sponsored by AbbVie and will explore the effects of Icalcaprant Dose A and Icalcaprant Dose B, targeting an enrollment of 195 participants.
Where to Participate
Clinical trials for Icalcaprant are currently being conducted across a wide geographic area, making participation accessible to many individuals. There are 64 study sites located in 46 cities across 15 states in the United States. This broad reach helps ensure diverse representation among participants.
The top locations with multiple study sites include:
- New York, New York (3 sites)
- Austin, Texas (3 sites)
- Orlando, Florida (3 sites)
- Columbus, Ohio (2 sites)
- Oklahoma City, Oklahoma (2 sites)
- Atlanta, Georgia (2 sites)
- Chicago, Illinois (2 sites)
- Warrenville, Illinois (2 sites)
- Richardson, Texas (2 sites)
- Hollywood, Florida (2 sites)
To be eligible for these studies, participants must be between 18 and 65 years of age. Both male and female individuals are welcome to join. It is important to note that these trials are not seeking healthy volunteers; participants must have a diagnosis of the specific condition being studied. Additionally, these studies are designed for adults and do not include children.
Development Timeline
The journey of Icalcaprant began with its first clinical trial initiated on November 20, 2024, marking the start of its formal investigation. Since then, the development program has steadily advanced, with the latest trial starting on December 11, 2025. All four clinical trials conducted to date have been sponsored by AbbVie, demonstrating a consistent commitment to exploring Icalcaprant's potential.
Initially, Icalcaprant was studied for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. As research progressed, the focus expanded to address significant unmet needs in mental health. The development pipeline broadened to include studies for Bipolar II Disorder and Major Depressive Disorder, reflecting a strategic shift towards neurological and psychiatric indications. The program has progressed through early-stage research, with two Phase 1 trials completed, and is now actively engaged in two Phase 2 trials. These studies have collectively enrolled 418 participants, gathering crucial data as Icalcaprant moves through the rigorous process of drug development.