Obesity, Overweight and Obesity, Weight Loss
Conditions
Keywords
Obesity, Overweight, Thermogenesis, Fat reduction
Brief summary
Obesity is a direct result of food-intake in excess of body energy expenditure. Thus, induction of increased energy expenditure via the activation of thermogenesis at targeted anatomical sites can counterbalance obesity. This trial aims to study RZL-012, a novel compound, in treating obesity by activating thermogenesis in subcutaneous fat.
Detailed description
Obesity is a direct result of food-intake in excess of body energy expenditure. Therefore, a feasible approach to combat obesity is via energy-consuming activities, such as physical exercise. Unfortunately, our modern society is moving in the other direction, spending more time in immobilized positions, at work and at home. An alternative strategy for the induction of increased energy expenditure is via the activation of thermogenic cells that utilize fat to produce heat.RZL-012 is a novel molecule that enables de-novo generation of thermogenic tissue at favorable anatomical sites. As a result, the extra fat accumulated in obese persons will be turned into heat. This is a double blind, randomized, placebo controlled, dose escalation Phase 2a clinical trial for the evaluation of safety, efficacy and thermogenesis-induction of RZL-012 in overweight and obese volunteers. This trial aims to study the ability of RZL-012 in treating obesity via the induction of thermogenic foci in subcutaneous fat.
Interventions
DRUGRZL-012
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat.
DRUGPlacebo
Subject receive a single-time injection. Multiple injections of the Placebo are administered at 8-36 sites (0.1mL per site) into the abdominal subcutaneous fat.
Sponsors
Spaulding Clinical Research LLC
Raziel Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double Blind, Randomized, Placebo Controlled
Intervention model description
This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adult male subjects, 20-60 years old. 2. Subject is considered overweight and obese, with 27.5 \< BMI ≤ 34.9. 3. Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9. 4. Subjects with stable weight in the last 3 months by medical history. 5. Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa. 6. Generally considered healthy according to medical history, physical examination, electrocardiogram (ECG) and laboratory evaluation with a special emphasis on metabolic parameters (fasting glucose concentration \< 100 mg, normal blood pressure). 7. Subject is willing to refrain from sexual activity or agrees to use a double-barrier contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with RZL 012. 8. Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study. 9. Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.
Exclusion criteria
1. Subjects weighing less than 75 kg. 2. Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months. 3. Unable to tolerate subcutaneous injection. 4. Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator put the subject at significant risk, are not eligible. 5. Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible. 6. Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible. 7. As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study. 8. Medication use on regular basis. 9. Positive drug and alcohol tests. 10. Known sensitivity to components of the injection formulation. 11. Prior wound, tattoo or infection in the treated area. 12. Excessive growth of hair in the abdomen region. 13. Claustrophobia or MRI incompatible device or implant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: The Incidence of Treatment-related Adverse Events [AEs] | 0-168 days | AEs will be assessed by significant clinical changes in safety parameter (e.g. vital signs, ECG, clinical laboratory evaluations)AEs incidence will be by body system, seriousness, severity and relation to study drug by cohort. |
| Efficacy: A Significant Thermogenesis at the Injected Site. | 28-168 days | Thermogenesis is measured by thermal imaging is non-invasive, non-radiating Infra-Red thermal camera that passively measures the emitting infra-red radiation of body surface. Difference in temperatures between the sites (treated - not treated) by visit treatment along with the change from baseline (net-delta) in these differences by cohort and overall. Significant thermogenesis is defined as net-delta ≥ 1. Outcome measure data table represents the number of subjects who demonstrated an increase that is higher than 1 celsius degree. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Fasting Blood Glucose From Baseline. | 56 days | Changes from baseline in fasting blood glucose by visit, treatment, and cohort. |
| Changes in Blood Lipid Profile From Baseline. | 56 days | Changes from baseline in lipid profile by visit, treatment, and cohort. |
| Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 1-2 days | Averaged Cmax values by cohort. |
| Duration of the Thermogenic Effect From Day 28. | 28-168 days | The duration of the thermogenic effect for subjects in the active arm with thermogenic effect (net-delta ≥ 1) by visit and cohort. |
| Changes in Waist to Hip Ratio [WHR] | 56 days | Changes from baseline in WHR by visit, treatment, and cohort. WHR is calculated by measurements of waist circumference and hip circumference. |
| Elucidation of the Histological Changes Account for the Thermogenic Effect. | 56 days | An abdominal subcutaneous adipose tissue biopsy will be taken from the injected side. Histology results will be assessed for 2 subjects who were injected with 120 mg RZL-012 and for one subject who was injected with placebo. |
| Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | 28 days | Changes from baseline in inflammatory markers and cytokines by visit, treatment, and cohort. Testing of inflammatory markers and cytokines will be conducted by blood sampling. |
| Changes in Body Weight | 56 days | Changes from baseline in body weight by visit, treatment, and cohort. |
| Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | 28-168 days | Subcutaneous Fat Mass (SFM) ratio (treated sites / control sites) averaged over the MRI slices by visit, treatment and cohort and the change from baseline in SFM ratio (in % from the ratio at baseline) compared between the treatment arms. |
Countries
United States
Participant flow
Pre-assignment details
Study was designed to enroll 32 subjects. In practice, 33 subjects were enrolled into the study. In cohort 3, one subject that was injected with plcebo was lost to follow up 3 days following injection. Therefore, an additional subject was enrolled and injected with placebo but he also was lost to follow up, 7 days following injection.
Participants by arm
| Arm | Count |
|---|---|
| RZL-012 Cohort 1 A single-time injection, multiple subcutaneous injections of 40mg RZL-012 administered into 8 sites (0.1mL per site):
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 8 (0.1mL per site) into the abdominal subcutaneous fat. | 6 |
| RZL-012 Cohort 2 A single-time injection, multiple subcutaneous injections of 80mg RZL-012 administered into 16 sites (0.1mL per site):
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 16(0.1mL per site) into the abdominal subcutaneous fat. | 6 |
| RZL-012 Cohort 3 A single-time injection, multiple subcutaneous injections of 120mg RZL-012 administered into 24 sites (0.1mL per site):
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 24(0.1mL per site) into the abdominal subcutaneous fat. | 6 |
| RZL-012 Cohort 4 A single-time injection, multiple subcutaneous injections of 180mg RZL-012 administered into 36 sites (0.1mL per site):
Subject receive a single-time injection. Multiple injections of RZL-012 are administered at 36(0.1mL per site) into the abdominal subcutaneous fat. | 6 |
| Placebo A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site)
Placebo: Subject receive a single-time injection. Multiple injections of the Placebo are administered at8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. | 9 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 33 Participants |
| Age, Continuous | 31.7 years STANDARD_DEVIATION 2.1 | 44.5 years STANDARD_DEVIATION 12.1 | 40 years STANDARD_DEVIATION 11.8 | 41.7 years STANDARD_DEVIATION 13.2 | 39.2 years STANDARD_DEVIATION 10.3 | 39.4 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 8 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 9 participants | 33 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 9 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
Outcome results
Primary
Efficacy: A Significant Thermogenesis at the Injected Site.
Thermogenesis is measured by thermal imaging is non-invasive, non-radiating Infra-Red thermal camera that passively measures the emitting infra-red radiation of body surface. Difference in temperatures between the sites (treated - not treated) by visit treatment along with the change from baseline (net-delta) in these differences by cohort and overall. Significant thermogenesis is defined as net-delta ≥ 1. Outcome measure data table represents the number of subjects who demonstrated an increase that is higher than 1 celsius degree.
Time frame: 28-168 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 56 | 1 Participants |
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 140 | NA Participants |
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 112 | NA Participants |
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 84 | NA Participants |
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 168 | NA Participants |
| RZL-012 Cohort 1 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 28 | 5 Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 28 | 5 Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 140 | NA Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 168 | NA Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 56 | 3 Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 84 | NA Participants |
| RZL-012 Cohort 2 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 112 | NA Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 168 | NA Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 112 | NA Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 84 | NA Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 28 | 3 Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 140 | NA Participants |
| RZL-012 Cohort 3 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 56 | 3 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 140 | 4 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 168 | 3 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 28 | 6 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 56 | 6 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 84 | 4 Participants |
| RZL-012 Cohort 4 | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 112 | 5 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 168 | 0 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 28 | 1 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 84 | 0 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 112 | 0 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 140 | 0 Participants |
| Placebo | Efficacy: A Significant Thermogenesis at the Injected Site. | Day 56 | 0 Participants |
Primary
Safety: The Incidence of Treatment-related Adverse Events [AEs]
AEs will be assessed by significant clinical changes in safety parameter (e.g. vital signs, ECG, clinical laboratory evaluations)AEs incidence will be by body system, seriousness, severity and relation to study drug by cohort.
Time frame: 0-168 days
Population: 20-60 years old, overweight and obese by BMI definition (27.5 \< BMI ≤ 34.9), adult males.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - hemorrhage | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - pain | 6 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition medical device reac | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - injection mass | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - erythema | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - warmth | 2 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - nodule | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - rash | 1 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- Edema | 6 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Cardiac disorder ventricular extrasystoles | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- pruritus | 2 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Rhinorrhoea | 1 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Ear pain | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Respiratory tracongestion | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders Ear swelling | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - pruritus | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - oropharyngea pain | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Hypoacusis | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders - Headache | 2 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders otorrhoea | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders hyperhidros | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders- Dizziness | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - energy uncreased | 1 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Serious Adverse Events | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - pain extre | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - feeling hot | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - Fatifue | 1 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - myalgia | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - bruising | 1 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Investigations - Electrodiagram QT prolonged | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - discolourization | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Other Adverse Events | 6 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Injury and procedure complications - skin abrasion | 0 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - Erythema | 6 participants |
| RZL-012 Cohort 1 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | general condition non cardiac chest pain | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Hypoacusis | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - hemorrhage | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders hyperhidros | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition medical device reac | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - warmth | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders- Dizziness | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - injection mass | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - Erythema | 6 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders otorrhoea | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - rash | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Investigations - Electrodiagram QT prolonged | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - nodule | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Rhinorrhoea | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Other Adverse Events | 6 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- pruritus | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - pain extre | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- Edema | 4 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - bruising | 1 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - energy uncreased | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Cardiac disorder ventricular extrasystoles | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - pain | 5 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - erythema | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Respiratory tracongestion | 1 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - Fatifue | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Ear pain | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - pruritus | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Serious Adverse Events | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - oropharyngea pain | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | general condition non cardiac chest pain | 1 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders Ear swelling | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - myalgia | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - discolourization | 0 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Injury and procedure complications - skin abrasion | 1 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders - Headache | 1 participants |
| RZL-012 Cohort 2 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - feeling hot | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Respiratory tracongestion | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - pain | 5 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Serious Adverse Events | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Other Adverse Events | 6 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Cardiac disorder ventricular extrasystoles | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Ear pain | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders Ear swelling | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Hypoacusis | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders otorrhoea | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - energy uncreased | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - Fatifue | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - feeling hot | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - bruising | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - discolourization | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - Erythema | 4 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - hemorrhage | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - injection mass | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - nodule | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- Edema | 6 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- pruritus | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - rash | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - warmth | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition medical device reac | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | general condition non cardiac chest pain | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Injury and procedure complications - skin abrasion | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Investigations - Electrodiagram QT prolonged | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - myalgia | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - pain extre | 0 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders- Dizziness | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders - Headache | 2 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - oropharyngea pain | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Rhinorrhoea | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - erythema | 3 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders hyperhidros | 1 participants |
| RZL-012 Cohort 3 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - pruritus | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | general condition non cardiac chest pain | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Hypoacusis | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Investigations - Electrodiagram QT prolonged | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders hyperhidros | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders - Headache | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - hemorrhage | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders Ear swelling | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - feeling hot | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - discolourization | 1 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - oropharyngea pain | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - Erythema | 5 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Ear pain | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - myalgia | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - energy uncreased | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Respiratory tracongestion | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - erythema | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Cardiac disorder ventricular extrasystoles | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - Fatifue | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Injury and procedure complications - skin abrasion | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Serious Adverse Events | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - pain | 5 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - pain extre | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- Edema | 4 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - bruising | 2 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Rhinorrhoea | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- pruritus | 2 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - warmth | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - nodule | 1 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders otorrhoea | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition medical device reac | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - rash | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - pruritus | 1 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - injection mass | 1 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders- Dizziness | 0 participants |
| RZL-012 Cohort 4 | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Other Adverse Events | 6 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- pruritus | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - Erythema | 8 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition medical device reac | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - discolourization | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - pruritus | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | general condition non cardiac chest pain | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - bruising | 3 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Injury and procedure complications - skin abrasion | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - feeling hot | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders - erythema | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Investigations - Electrodiagram QT prolonged | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - Fatifue | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Serious Adverse Events | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - myalgia | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders otorrhoea | 2 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | skin and subcutaneous tissue disorders hyperhidros | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Muscoloskeletal and connective tissue - pain extre | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Hypoacusis | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders- Dizziness | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders Ear swelling | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Nervou system disorders - Headache | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Ear and labyrinth disorders - Ear pain | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - warmth | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - oropharyngea pain | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Cardiac disorder ventricular extrasystoles | 1 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Respiratory tracongestion | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Other Adverse Events | 9 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Aministration site condition - energy uncreased | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition- Edema | 5 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - pain | 3 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - nodule | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - injection mass | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Respeiratory, thoracic - Rhinorrhoea | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - rash | 0 participants |
| Placebo | Safety: The Incidence of Treatment-related Adverse Events [AEs] | Administration site condition - hemorrhage | 0 participants |
Secondary
Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling.
Changes from baseline in inflammatory markers and cytokines by visit, treatment, and cohort. Testing of inflammatory markers and cytokines will be conducted by blood sampling.
Time frame: 28 days
Population: The study was designed in a way that inflammation marker will be measured only for active and placebo subjects from cohorts 2-4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day 28 (mg/dL) | 0.27 mg/dL | Standard Deviation 0.31 |
| RZL-012 Cohort 1 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day -1 (mg/dL) | 0.2 mg/dL | Standard Deviation 0.13 |
| RZL-012 Cohort 2 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day 28 (mg/dL) | 0.2 mg/dL | Standard Deviation 0.12 |
| RZL-012 Cohort 2 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day -1 (mg/dL) | 0.6 mg/dL | Standard Deviation 1.08 |
| RZL-012 Cohort 3 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day 28 (mg/dL) | 0.43 mg/dL | Standard Deviation 0.15 |
| RZL-012 Cohort 3 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day -1 (mg/dL) | 0.5 mg/dL | Standard Deviation 0 |
| RZL-012 Cohort 4 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day -1 (mg/dL) | 0.2 mg/dL | Standard Deviation 0.1 |
| RZL-012 Cohort 4 | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. | CRP Day 28 (mg/dL) | 0.2 mg/dL | Standard Deviation 0.1 |
p-value: >0.05t-test, 2 sided
Secondary
Changes in Blood Lipid Profile From Baseline.
Changes from baseline in lipid profile by visit, treatment, and cohort.
Time frame: 56 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day -1 | 188 mg/dL | Standard Deviation 32.8 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day 56 | 184 mg/dL | Standard Deviation 39.8 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | HDL Day -1 | 43.5 mg/dL | Standard Deviation 7.23 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | HDL Day 56 | 40 mg/dL | Standard Deviation 9.44 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | LDL Day -1 | 129 mg/dL | Standard Deviation 33.5 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | LDL Day 56 | 120 mg/dL | Standard Deviation 31.3 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day -1 | 107.3 mg/dL | Standard Deviation 42.3 |
| RZL-012 Cohort 1 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day 56 | 118 mg/dL | Standard Deviation 85.4 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | HDL Day -1 | 44.33 mg/dL | Standard Deviation 11.1 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | LDL Day 56 | 132 mg/dL | Standard Deviation 23.9 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day -1 | 199 mg/dL | Standard Deviation 11 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | HDL Day 56 | 50.8 mg/dL | Standard Deviation 14.2 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day 56 | 205 mg/dL | Standard Deviation 29.7 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day 56 | 136 mg/dL | Standard Deviation 61.1 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | LDL Day -1 | 126.5 mg/dL | Standard Deviation 13.3 |
| RZL-012 Cohort 2 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day -1 | 131 mg/dL | Standard Deviation 77 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day -1 | 112.5 mg/dL | Standard Deviation 58.9 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day 56 | 193.5 mg/dL | Standard Deviation 16.7 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | HDL Day 56 | 41.5 mg/dL | Standard Deviation 9.9 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | LDL Day 56 | 134.7 mg/dL | Standard Deviation 37 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | HDL Day -1 | 41.5 mg/dL | Standard Deviation 6 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day 56 | 201.7 mg/dL | Standard Deviation 46.1 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day -1 | 196 mg/dL | Standard Deviation 41.4 |
| RZL-012 Cohort 3 | Changes in Blood Lipid Profile From Baseline. | LDL Day -1 | 134 mg/dL | Standard Deviation 33 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day 56 | 176 mg/dL | Standard Deviation 28.6 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | HDL Day -1 | 44 mg/dL | Standard Deviation 6.87 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | HDL Day 56 | 45.3 mg/dL | Standard Deviation 5.05 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | LDL Day -1 | 105.5 mg/dL | Standard Deviation 15 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | LDL Day 56 | 128 mg/dL | Standard Deviation 0 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day 56 | 128.33 mg/dL | Standard Deviation 55.4 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day -1 | 170.8 mg/dL | Standard Deviation 23 |
| RZL-012 Cohort 4 | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day -1 | 121.7 mg/dL | Standard Deviation 39.3 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | HDL Day 56 | 41.14 mg/dL | Standard Deviation 7 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day 56 | 234 mg/dL | Standard Deviation 220 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | HDL Day -1 | 42.44 mg/dL | Standard Deviation 5.6 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | Triglycerides Day -1 | 155.8 mg/dL | Standard Deviation 98 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day -1 | 186.7 mg/dL | Standard Deviation 19.8 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | LDL Day 56 | 103 mg/dL | Standard Deviation 14.8 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | Cholesterol Day 56 | 182.4 mg/dL | Standard Deviation 19.3 |
| Placebo | Changes in Blood Lipid Profile From Baseline. | LDL Day -1 | 116 mg/dL | Standard Deviation 10.3 |
Secondary
Changes in Body Weight
Changes from baseline in body weight by visit, treatment, and cohort.
Time frame: 56 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Changes in Body Weight | Weight Day -1 | 103.3 Kg | Standard Deviation 11.1 |
| RZL-012 Cohort 1 | Changes in Body Weight | Weight Day 56 | 104.4 Kg | Standard Deviation 12.5 |
| RZL-012 Cohort 2 | Changes in Body Weight | Weight Day -1 | 95.4 Kg | Standard Deviation 6.9 |
| RZL-012 Cohort 2 | Changes in Body Weight | Weight Day 56 | 96.1 Kg | Standard Deviation 7.8 |
| RZL-012 Cohort 3 | Changes in Body Weight | Weight Day -1 | 101.3 Kg | Standard Deviation 20.3 |
| RZL-012 Cohort 3 | Changes in Body Weight | Weight Day 56 | 103.4 Kg | Standard Deviation 22.4 |
| RZL-012 Cohort 4 | Changes in Body Weight | Weight Day 56 | 96 Kg | Standard Deviation 12.3 |
| RZL-012 Cohort 4 | Changes in Body Weight | Weight Day -1 | 96.1 Kg | Standard Deviation 12.6 |
| Placebo | Changes in Body Weight | Weight Day -1 | 99.1 Kg | Standard Deviation 8.1 |
| Placebo | Changes in Body Weight | Weight Day 56 | 101.2 Kg | Standard Deviation 9.7 |
Secondary
Changes in Fasting Blood Glucose From Baseline.
Changes from baseline in fasting blood glucose by visit, treatment, and cohort.
Time frame: 56 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Changes in Fasting Blood Glucose From Baseline. | Day -1 | 86.7 mg/dL | Standard Deviation 4.2 |
| RZL-012 Cohort 1 | Changes in Fasting Blood Glucose From Baseline. | Day 56 | 93 mg/dL | Standard Deviation 3.22 |
| RZL-012 Cohort 2 | Changes in Fasting Blood Glucose From Baseline. | Day -1 | 91.3 mg/dL | Standard Deviation 5.16 |
| RZL-012 Cohort 2 | Changes in Fasting Blood Glucose From Baseline. | Day 56 | 92.8 mg/dL | Standard Deviation 11.8 |
| RZL-012 Cohort 3 | Changes in Fasting Blood Glucose From Baseline. | Day -1 | 91.7 mg/dL | Standard Deviation 7.47 |
| RZL-012 Cohort 3 | Changes in Fasting Blood Glucose From Baseline. | Day 56 | 93.3 mg/dL | Standard Deviation 7.58 |
| RZL-012 Cohort 4 | Changes in Fasting Blood Glucose From Baseline. | Day 56 | 93.7 mg/dL | Standard Deviation 5.3 |
| RZL-012 Cohort 4 | Changes in Fasting Blood Glucose From Baseline. | Day -1 | 90.8 mg/dL | Standard Deviation 7.17 |
| Placebo | Changes in Fasting Blood Glucose From Baseline. | Day -1 | 93.2 mg/dL | Standard Deviation 3.93 |
| Placebo | Changes in Fasting Blood Glucose From Baseline. | Day 56 | 94.6 mg/dL | Standard Deviation 6.6 |
p-value: >0.05t-test, 2 sided
p-value: >0.05t-test, 2 sided
p-value: >0.05t-test, 2 sided
p-value: >0.05t-test, 2 sided
Secondary
Changes in Waist to Hip Ratio [WHR]
Changes from baseline in WHR by visit, treatment, and cohort. WHR is calculated by measurements of waist circumference and hip circumference.
Time frame: 56 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day -1 | 1 ratio | Standard Error 0.1 |
| RZL-012 Cohort 1 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day 56 | 1 ratio | Standard Error 0 |
| RZL-012 Cohort 2 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day -1 | 1 ratio | Standard Error 0 |
| RZL-012 Cohort 2 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day 56 | 1 ratio | Standard Error 0 |
| RZL-012 Cohort 3 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day -1 | 1 ratio | Standard Error 0.1 |
| RZL-012 Cohort 3 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day 56 | 1 ratio | Standard Error 0 |
| RZL-012 Cohort 4 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day 56 | 1 ratio | Standard Error 0 |
| RZL-012 Cohort 4 | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day -1 | 1 ratio | Standard Error 0 |
| Placebo | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day -1 | 1 ratio | Standard Error 0.1 |
| Placebo | Changes in Waist to Hip Ratio [WHR] | Waist to hip ratio Day 56 | 1 ratio | Standard Error 0.1 |
Secondary
Duration of the Thermogenic Effect From Day 28.
The duration of the thermogenic effect for subjects in the active arm with thermogenic effect (net-delta ≥ 1) by visit and cohort.
Time frame: 28-168 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 Cohort 1 | Duration of the Thermogenic Effect From Day 28. | 5.6 days | Standard Deviation 12.5 |
| RZL-012 Cohort 2 | Duration of the Thermogenic Effect From Day 28. | 16.8 days | Standard Deviation 15.3 |
| RZL-012 Cohort 3 | Duration of the Thermogenic Effect From Day 28. | 5.6 days | Standard Deviation 12.5 |
| RZL-012 Cohort 4 | Duration of the Thermogenic Effect From Day 28. | 107.3 days | Standard Deviation 44.9 |
| Placebo | Duration of the Thermogenic Effect From Day 28. | 0 days | Standard Deviation 0 |
Secondary
Elucidation of the Histological Changes Account for the Thermogenic Effect.
An abdominal subcutaneous adipose tissue biopsy will be taken from the injected side. Histology results will be assessed for 2 subjects who were injected with 120 mg RZL-012 and for one subject who was injected with placebo.
Time frame: 56 days
Population: Biopsy was done only for 2 active and 1 placebo subjects in cohort 3. Biopsy was not done in subjects from cohorts 1,2 or 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 Cohort 1 | Elucidation of the Histological Changes Account for the Thermogenic Effect. | 2 Participants |
| RZL-012 Cohort 2 | Elucidation of the Histological Changes Account for the Thermogenic Effect. | 1 Participants |
Secondary
Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen.
Subcutaneous Fat Mass (SFM) ratio (treated sites / control sites) averaged over the MRI slices by visit, treatment and cohort and the change from baseline in SFM ratio (in % from the ratio at baseline) compared between the treatment arms.
Time frame: 28-168 days
Population: In cohort 4, one subjects was not analyzed due to MRI image quality (bubble)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 168 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 84 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 140 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 112 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 28 | -0.62 percentage of SFM reduction | Standard Deviation 5.17 |
| RZL-012 Cohort 1 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 56 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 28 | -9.15 percentage of SFM reduction | Standard Deviation 10.55 |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 56 | -8.56 percentage of SFM reduction | Standard Deviation 8.85 |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 84 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 112 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 140 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 2 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 168 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 56 | -10.52 percentage of SFM reduction | Standard Deviation 8.42 |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 140 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 28 | -9.1 percentage of SFM reduction | Standard Deviation 4.27 |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 84 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 168 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 3 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 112 | NA percentage of SFM reduction | — |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 168 | -14.32 percentage of SFM reduction | Standard Deviation 10.94 |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 84 | -12.75 percentage of SFM reduction | Standard Deviation 9.83 |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 112 | -16.10 percentage of SFM reduction | Standard Deviation 13.81 |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 28 | -14.68 percentage of SFM reduction | Standard Deviation 8.16 |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 140 | -12.46 percentage of SFM reduction | Standard Deviation 11.26 |
| RZL-012 Cohort 4 | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 56 | -18.10 percentage of SFM reduction | Standard Deviation 10.93 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 140 | -2.9 percentage of SFM reduction | Standard Deviation 0.45 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 28 | 2.94 percentage of SFM reduction | Standard Deviation 10.08 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 168 | -2.54 percentage of SFM reduction | Standard Deviation 8.57 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 56 | 3.61 percentage of SFM reduction | Standard Deviation 3.48 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 112 | -8.2 percentage of SFM reduction | Standard Deviation 11.54 |
| Placebo | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. | Day 84 | -6.57 percentage of SFM reduction | Standard Deviation 9.78 |
Comparison: The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groupsp-value: >0.05Kruskal-Wallis
Comparison: The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups, at day 28 and Day 56p-value: <0.05Kruskal-Wallis
Comparison: The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groupsp-value: <0.05Kruskal-Wallis
Comparison: The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groupsp-value: <0.05Kruskal-Wallis
Secondary
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Tmax values by cohort.
Time frame: 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 Cohort 1 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 1.83 Hour | Standard Deviation 0.41 |
| RZL-012 Cohort 2 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 1.83 Hour | Standard Deviation 0.41 |
| RZL-012 Cohort 3 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 1.83 Hour | Standard Deviation 0.41 |
| RZL-012 Cohort 4 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 2 Hour | Standard Deviation 0 |
Secondary
Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012.
Averaged Cmax values by cohort.
Time frame: 1-2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 Cohort 1 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 84.15 ng/mL | Standard Deviation 16.27 |
| RZL-012 Cohort 2 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 181.89 ng/mL | Standard Deviation 49.86 |
| RZL-012 Cohort 3 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 241 ng/mL | Standard Deviation 72.09 |
| RZL-012 Cohort 4 | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. | 344 ng/mL | Standard Deviation 73.7 |