A Randomized SAD and MAD Study Evaluating the Safety and Tolerability of RPh201 in Healthy Subjects and in Adults With Alzheimer's Disease

Regenera Pharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Healthy Volunteers; Moderate to Severe Alzheimer Patients

Treatments: Drug: Placebo; Drug: RPh201, botanical drug product

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01513967

RGN-ADC-001

Details and patient eligibility

About

This is a dual-centre, Phase I/IIa study, in healthy subjects and subjects with AD to investigate the safety, tolerability, cognitive, and behavioural effects of RPh201. The study will be divided into three parts: A, B, and C (NOT Performed)

Full description

The primary objective of this study is to evaluate the safety and tolerability of RPh201 after single and multiple ascending doses. This study is designed with sufficient time in between dose escalations to allow for an interim analysis of safety and tolerability data as this is considered the safest approach to assess the effects of a compound with an undefined mechanism and therapeutic target.

This protocol is written with some flexibility to accommodate the inherent dynamic nature of Phase I clinical studies. Modifications to the dose, dosing regimen, and/or clinical or laboratory procedures currently outlined below may be required to achieve the scientific goals of the study objectives and/or to ensure appropriate safety monitoring of the study subjects. Interim safety analyses will guide dose escalation/reduction in the trial.

Enrollment: 39 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

For PART A AND PART B (healthy volunteers, SAD and MAD)

Inclusion Criteria:

• healthy male or female subjects 18 to 65 years of age, inclusive
• body mass index (BMI) within the range of 18.0 to 33.0 kg/m2, inclusive, and a minimum weight of at least 50.0 kg at Screening
• female subjects of childbearing potential must be practicing abstinence or using and willing to continue using two medically acceptable form of birth control for at least 1 month prior to Screening (at least 3 months for oral and transdermal contraceptives) and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include oral or patch hormonal contraceptives, intrauterine device, progestin implant or injection, bilateral tubal ligation, or double-barrier (i.e., male condom in addition to a diaphragm or a contraceptive sponge).
• female subjects of non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by subject medical history)
• male subjects of reproductive potential with a partner(s) of childbearing potential, must be using and willing to continue to using two medically acceptable contraceptive precautions from Screening and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include abstinence, vasectomy, or male condom for subjects
• female subjects must have a negative pregnancy test
• able to speak, read, and understand English sufficiently to understand the nature of the study, to provide written informed consent, and to allow completion of all study assessments
• must understand and provide written informed consent prior to the initiation of any protocol-specific procedures
• must be willing and able to abide by all study requirements and restrictions

Exclusion Criteria:

• current drug or alcohol dependence (excluding caffeine), based on self-report, including subjects who have been in a drug rehabilitation program
• current smoker or a history of using tobacco products within 3 months prior to Screening
• clinically significant abnormalities on physical examination, medical history, 12-lead ECG (i.e., QTc > 440 for male subjects and > 450 for female subjects), vital signs, or laboratory values, as judged by the investigator or designee
• history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results
• use of a non-prescription drug within 7 days prior to the first drug administration. Subjects who have taken over-the-counter medication may still be entered into the study, if in the opinion of the investigator or designee, the medication received will not interfere with the study procedures or data integrity or compromise the safety of the subject
• use of any prescription medications, recreational drugs, or natural health products (except vitamin or mineral supplements, acceptable forms of birth control, and hormone replacement) within 14 days prior to first drug administration or throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity or compromise the safety of the subject
• positive urine drug screen
• positive breath alcohol test. If a subject presents with positive breath alcohol test, the subject may be rescheduled at the discretion of the investigator or designee
• female subjects who are currently pregnant or lactating or who are planning to become pregnant within 60 days of last study drug administration
• history of allergy or hypersensitivity to mastic or related drugs (e.g., mastic gum, mastic resin, Chios mastic powder, retsina wine, Mastic Gum 500, Mastic Gum Elma 50, Nutricology Mastic Gum)
• history of allergy or hypersensitivity to cottonseed oil
• positive for Hepatitis B, Hepatitis C, or HIV
• current or pending legal charges or currently on probation
• treatment with any investigational drug within 30 days prior to first drug administration in the treatment phase
• a subject who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study protocol for any reason

For PART C (subjects with Alzheimer's Disease)

Inclusion Criteria:

• males and females ages ≥ 55 years of age at Screening visit
• diagnosis of AD, consistent with criteria from both the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) Criteria for Probable AD and Diagnostic and Statistical Manual of Mental Disorders - IV TR (DSM-IV TR) Criteria for Dementia of the Alzheimer's Type
• Mini-Mental Status Evaluation (MMSE) score of 5-15, inclusive, at Screening visit
• Rosen-Modified Hachninski Ischemia score of ≤ 4 at Screening visit
• subjects and caregivers must be able to read, write, and speak the language in which psychometric tests are provided with acceptable visual and auditory acuity
• subject must have a reliable informant (caregiver) to provide collateral history and who will facilitate the subject's full participation in the study
• subject and caregivers must provide written informed consent and be willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
• subjects may continue on background cholinesterase inhibitor and/or memantine
• subjects must be in satisfactory good health, in the opinion of the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory tests
• magnetic resonance imaging (MRI) or computed tomography (CT) within 12 months of Screening visit consistent with a diagnosis of Probable AD without any other clinically significant findings

Exclusion Criteria:

• diagnosis or history of other dementia or neurodegenerative disorders causing cognitive impairment (e.g., Parkinson's disease, Lewy body disease, Fronto-temporal Dementia, alcohol and drug abuse, Traumatic Brain Injury).
• subjects receiving immunosuppressants, tricyclic anti-depressants, anticoagulants, or chemotherapeutic agents
• hypertension not adequately controlled, per investigator's judgment
• poorly controlled Type 1 and/or Type 2 diabetes, per investigator's judgment
• women of child bearing potential who are not using an effective method of birth control
• any other medical condition or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or that may interfere with the interpretation of study results, and that, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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39 participants in 12 patient groups, including a placebo group

Part A, SAD Treatment 1

Experimental group

Description:

RPh201 single dose (SAD Low Dose )

Treatment:

Drug: RPh201, botanical drug product

Part A, SAD Placebo 1

Placebo Comparator group

Description:

Placebo single dose (SAD Low Dose )

Treatment:

Drug: Placebo

Part A, SAD Treatment 2

Experimental group

Description:

RPh201 single dose (SAD Mid Dose )

Treatment:

Drug: RPh201, botanical drug product

Part A, SAD Placebo 2

Placebo Comparator group

Description:

Placebo single dose (SAD Mid Dose )

Treatment:

Drug: Placebo

Part A, SAD Treatment 3

Experimental group

Description:

RPh201 single dose (SAD High Dose )

Treatment:

Drug: RPh201, botanical drug product

Part A, SAD Placebo 3

Placebo Comparator group

Description:

Placebo single dose (SAD High Dose )

Treatment:

Drug: Placebo

Part B, MAD Treatment 1

Experimental group

Description:

RPh201 multiple dose (MAD Low Dose )

Treatment:

Drug: RPh201, botanical drug product

Part B, MAD Placebo 1

Placebo Comparator group

Description:

Placebo multiple dose (MAD Low Dose )

Treatment:

Drug: Placebo

Part B, MAD Treatment 2

Experimental group

Description:

RPh201 multiple dose (MAD Mid Dose )

Treatment:

Drug: RPh201, botanical drug product

Part B, MAD Placebo 2

Placebo Comparator group

Description:

Placebo multiple dose (MAD Mid Dose )

Treatment:

Drug: Placebo

Part B, MAD Treatment 3

Experimental group

Description:

RPh201 multiple dose (MAD High Dose )

Treatment:

Drug: RPh201, botanical drug product

Part B, MAD Placebo 3

Placebo Comparator group

Description:

Placebo multiple dose (MAD High Dose )

Treatment:

Drug: Placebo