IGC-AD1 Trial on Agitation in Dementia Due to Alzheimer's (IGC-AD1-P2)

• ClinicalTrials.gov Identifier: NCT05543681
• Recruitment Status: Recruiting
• First Posted: September 16, 2022
• Last Update Posted: January 8, 2024
• Sponsor: IGC Pharma LLC
• Information provided by (Responsible Party): India Globalization Capital Inc ( IGC Pharma LLC )

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy of an oral medication, IGC-AD1 that is a natural THC-based (Tetrahydrocannabinol) formulation, administered in micro doses, twice a day, on symptomatological Agitation, in patients with mild to severe dementia from Alzheimer's.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease; Agitation,Psychomotor; Depression; Anxiety; Memory Impairment; Care Giving Burden; NPS; Agitated; State, Acute Reaction to Stress; Aggression; Aggressive Outburst	Drug: Agitation management in Alzheimer's disease (IGC-AD1-Active); Drug: Agitation management in Alzheimer's disease (IGC-AD1-Placebo)	Phase 2

Detailed Description:

This is a placebo-controlled, multi-site, parallel, double blind, randomized study. Enrollment is open for Participants ages 60 and above with mild to severe dementia due to Alzheimer's Disease, with established symptomatological Agitation, for a minimum of two weeks prior to enrollment, with Agitation due to other etiologies, or recent, or transient Agitation symptoms ruled out. Clinical Agitation is established with a baseline NPI-12 (Agitation Domain only) score ≥ 4 as well as meeting the IPA criteria for Agitation.

The medication is titrated to BID over two days and down over two days at End of Trial (EOT). Caregivers will monitor and record in a logbook vitals daily using Sponsor provided scales and logbook.

Safety will be monitored with daily calls to the Participant/Caregiver dyad for the first four days followed by calls every third day till EOT. Week two is an on-site visit with week-four being optional.

Both solicited AEs and non-solicited AEs will be monitored, assessed, graded, and tabulated. Solicited AEs include the following: somnolence, falls, dizziness, asthenia, nausea, suicidal ideation, tachycardia, bradycardia, hypertension and hypotension, and BMI.

The primary objective of the study is to assess the efficacy of IGC-AD1 on Agitation as scored by the CMAI between baseline and EOT with the secondary objective being acute efficacy as measured by the CMAI between baseline and week two. There are several exploratory objectives included elsewhere. The trial will also have blood draws for sparse Pharmacokinetics (PK).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multi-site, Randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to severe dementia from Alzheimer's and symptomatological Agitation.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind for study site and participants
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Trial of the Safety and Efficacy of IGC-AD1 on Agitation in Participants With Dementia Due to Alzheimer's Disease
• Actual Study Start Date: October 11, 2022
• Estimated Primary Completion Date: June 30, 2025
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active Comparator: IGC-AD1Active; IGC-AD1 Active Treatment THC plus another API plus excipients.	Drug: Agitation management in Alzheimer's disease (IGC-AD1-Active); A non-sterile solution for oral administration.; Other Names: Active Study Drug; Study Drug; Active; IGC-AD1 Active
Placebo Comparator: Placebo Comparator: IGC-AD1 Placebo; IGC-AD1 Placebo, similar to Active in color, taste, and texture, with excipients but without APIs.	Drug: Agitation management in Alzheimer's disease (IGC-AD1-Placebo); A non-sterile solution for oral administration similar in color and texture to the Active.; Other Names: IGC-AD1 Placebo; Non-active study drug; IGC-AD1 Non-Active; Placebo

Outcome Measures

Primary Outcome Measures :

1. Agitation [ Time Frame: Baseline to week six ]
   Change in mean Cohen Mansfield Agitation Inventory (CMAI) score

Secondary Outcome Measures :

1. Acute Agitation [ Time Frame: Baseline to week two ]
   Change in mean Cohen Mansfield Agitation Inventory (CMAI) score

Other Outcome Measures:

1. Agitation at week four [ Time Frame: Baseline to week four ]
   Change in mean Cohen Mansfield Agitation Inventory (CMAI) score
2. Participant overall wellbeing [ Time Frame: Baseline to weeks two and six ]
   Change in the Clinical Global Impression Scale (CGI)
3. Participant executive functions [ Time Frame: Baseline to week six ]
   Change in Mini-Mental State Examination (MMSE2) score
4. Depression [ Time Frame: Baseline to weeks two, four, and six ]
   Change in mean Cornell Scale for Depression in Dementia (CSDD) score
5. Neuropsychiatric symptoms [ Time Frame: Baseline to weeks two, four, and six ]
   Change in mean Neuropsychiatric Inventory (NPI-12) score
6. Participant quality of life [ Time Frame: Baseline to weeks two, four and six ]
   Change in mean Quality of Life in Alzheimer's Disease (QOL-AD) score
7. Caregiver burden [ Time Frame: Baseline to weeks two and six ]
   Change in mean Zarit Burden Interview (ZBI) score
8. Psychotropic drugs [ Time Frame: Baseline to six weeks ]
   Change in type and dosage of psychotropic drugs
9. CYP2C9 polymorphisms on agitation [ Time Frame: Baseline to weeks two, four and six ]
   Change in mean Cohen Mansfield Agitation Inventory (CMAI) score for each type of metabolizer group (*1/*1, *1/*3, etc.)

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

To be eligible to participate in this study, the participant must meet all the following criteria:

Inclusion Criteria

1. Participant and/or Caregiver must provide a signed and dated ICF prior to any study procedures.
2. Must have a Caregiver who is able and willing to comply with all required study procedures.
3. The Caregiver must be known to the Participant and must be able to use electronic devices such as a cell phone, video conference over a laptop or cell phone, weighing scale, and be able to learn to take blood pressure, among others.
4. Based on local practice, Participants that cannot consent may have Caregiver's consent provided the Caregiver has among others a) Power of Attorney, b) is a spouse, or c) a sibling or d) a child or e) a close relation. The practice of accepting consent must be consistent with established practice at the site and jurisdiction.
5. Participants must consent to CYP450 and apolipoprotein E (ApoE) genotyping, and pharmacokinetics.
6. Diagnosis of AD by NIA-AA criteria

7. Clinically significant Agitation assessed by:

   1. NPI (Agitation) ≥ 4
   2. The presence of clinically significant, persistent Agitation based on the IPA definition (Appendix C) rather than those with recent onset and occasional symptoms, and
   3. Agitation not attributable to another psychiatric disorder, suboptimal care conditions, other underlining medical condition, or the physiological effects of a substance.
8. Negative drug screen, except for benzodiazepines if Participant has been using them in stable doses for at least 3 months before screening.
9. All medications used for behavioral symptoms should be consistent for at least 3 months before screening, with allowance for dose changes up to 25%.
10. Women must be of no childbearing potential (postmenopausal, defined as cessation of menses for at least 12 months, without an alternative medical cause for amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)).

An individual who meets any of the following criteria will be excluded from participation in this study:

Exclusion Criteria

1. Prior adverse reaction to cannabinoids or to any component of Study Drug (IGC-AD1 and placebo): THC, melatonin, honey, curcumin, ethyl alcohol, vitamin-E TPGS, ascorbic acid, water, tween-80, and rutin.
2. Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease, which might confound assessment of safety outcomes.
3. History of seizures, schizophrenia, or bipolar disorder.
4. Has participated in an investigational drug or device study within 30 days prior to study start.
5. Urine drug screen positive for drug use, except for benzodiazepines if Participant was using them previously and their dose had remained stable for at least 3 months before screening.
6. History of Alcohol and Drug use disorder, within one year prior to enrollment.
7. Hypertension: Participants with a history of uncontrolled hypertension as determined by the PI and Participants with a hypertensive crisis in the six months prior to enrollment.
8. Falls: Participants with a history of recurrent falls defined as more than two falls in the six-month period prior to enrollment and a history of falls resulting in injuries or associated with a new acute illness, loss of consciousness, fever, or abnormal blood pressure (Fuller et al., 2000).

Contacts and Locations

Contacts

Contact: Evelyn Gutierrez; 3013394270; egutierrez@igcpharma.com

Contact: Ram Mukunda, MS; 3015294996; ram@igcpharma.com

Locations

United States, Florida

Site 700; Recruiting

Melbourne, Florida, United States, 32940

Site 1200; Recruiting

Miami, Florida, United States, 33125

Site 1100; Recruiting

Port Charlotte, Florida, United States, 33952

United States, Maryland

Site 400; Recruiting

Baltimore, Maryland, United States, 21237

United States, Massachusetts

Site 800; Not yet recruiting

Newton, Massachusetts, United States, 02459

United States, New York

Site 900; Recruiting

Amherst, New York, United States, 02459

Contact: Site 900

Canada, Ontario

Site 1000; Recruiting

Toronto, Ontario, Canada, ON M6A 2E1

Canada, Quebec

Site 300; Active, not recruiting

Montréal, Quebec, Canada, H3Z 2Y5

Puerto Rico

Site 100; Recruiting

Bayamón, Puerto Rico, 00961

Site 200; Recruiting

Bayamón, Puerto Rico, 00961

Site 500; Recruiting

Rio Piedras, Puerto Rico, 00935

Sponsors and Collaborators

IGC Pharma LLC

Investigators

• Study Director: Dr. Saadia Shahnawaz, MD; IGC Pharma LLC

More Information

• Responsible Party: IGC Pharma LLC
• ClinicalTrials.gov Identifier: NCT05543681
• Other Study ID Numbers: IGC-AD1-P2 BIDAG
• First Posted: September 16, 2022
• Last Update Posted: January 8, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by India Globalization Capital Inc ( IGC Pharma LLC ):

Cannabis; Tetrahydrocannabinol; THC; Melatonin; Alzheimer's; Marijuana; Hemp; Agitation; Dementia; Depression; Anxiety; Memory; NPI; CMAI; Dronabinol

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Psychomotor Agitation; Depression; Aggression; Caregiver Burden; Stress Disorders, Traumatic, Acute; Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Aberrant Motor Behavior in Dementia; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Stress, Psychological; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders