Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers
Sponsor
Raziel Therapeutics Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT03171415
Collaborator
Spaulding Clinical Research LLC (Other)
32
1
2
17.1
1.9
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
This is a consecutive 4 cohort, dose escalation placebo-controlled clinical trialThis is a consecutive 4 cohort, dose escalation placebo-controlled clinical trial
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Double Blind, Randomized, Placebo Controlled
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date
:
Jul 25, 2017
Actual Primary Completion Date
:
Dec 28, 2018
Actual Study Completion Date
:
Dec 28, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RZL-012 A single-time injection, multiple subcutaneous injections of RZL-012 administered into 8-36 sites (0.1mL per site): 40mg RZL-012 -administered at 8 sites 80mg RZL-012 - administered at 16 sites 120mg RZL-012 - administered at 24 sites 180mg RZL-012 - administered at 36 sited |
Drug: RZL-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.
|
| Placebo Comparator: Placebo A single-time injection, multiple subcutaneous injections of Placebo administered into 8-36 sites (0.1mL per site) |
Drug: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- Changes in Body Weight [56 days]
Changes from baseline in body weight by visit, treatment, 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.
- Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. [0.5, 1,2,3,4,5,6,8,12,16,24,30 hours]
Averaged Tmax values by cohort.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 60 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Adult male subjects, 20-60 years old.
-
Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.
-
Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.
-
Subjects with stable weight in the last 3 months by medical history.
-
Not one of the following eating disorders by subject's declaration: anorexia nervosa, bulimia nervosa.
-
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).
-
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.
-
Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
-
Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.
Exclusion Criteria:
-
Subjects weighing less than 75 kg.
-
Subjects who have reduced/gained weight more than 5% of their current body weight in the last 3 months.
-
Unable to tolerate subcutaneous injection.
-
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.
-
Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) are not eligible.
-
Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible.
-
As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study.
-
Medication use on regular basis.
-
Positive drug and alcohol tests.
-
Known sensitivity to components of the injection formulation.
-
Prior wound, tattoo or infection in the treated area.
-
Excessive growth of hair in the abdomen region.
-
Claustrophobia or MRI incompatible device or implant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Spaulding Clinical | West Bend | Wisconsin | United States | 53095 |
Sponsors and Collaborators
- Raziel Therapeutics Ltd.
- Spaulding Clinical Research LLC
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Raziel Therapeutics Ltd.
ClinicalTrials.gov Identifier:
NCT03171415
Other Study ID Numbers:
- RZL-012-P2aUS-001
First Posted:
May 31, 2017
Last Update Posted:
Aug 21, 2019
Last Verified:
Sep 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Raziel Therapeutics Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | A single-time injection, multiple subcutaneous injections of 80 mg 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. | A single-time injection, multiple subcutaneous injections of 120 mg 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. | A single-time injection, multiple subcutaneous injections of 180 mg 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. | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| Period Title: Overall Study | |||||
| STARTED | 6 | 6 | 6 | 6 | 9 |
| COMPLETED | 6 | 6 | 6 | 6 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 9 | 33 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
33
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
31.7
(2.1)
|
44.5
(12.1)
|
40
(11.8)
|
41.7
(13.2)
|
39.2
(10.3)
|
39.4
(10.8)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
33
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
11.1%
|
2
6.1%
|
| Not Hispanic or Latino |
6
100%
|
5
83.3%
|
6
100%
|
6
100%
|
8
88.9%
|
31
93.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
33
100%
|
Outcome Measures
| Title | Safety: The Incidence of Treatment-related Adverse Events [AEs] |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 20-60 years old, overweight and obese by BMI definition (27.5 < BMI ≤ 34.9), adult males. |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 9 |
| Serious Adverse Events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Other Adverse Events |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
| Cardiac disorder ventricular extrasystoles |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Ear and labyrinth disorders - Ear pain |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Ear and labyrinth disorders Ear swelling |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Ear and labyrinth disorders - Hypoacusis |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Ear and labyrinth disorders otorrhoea |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
22.2%
|
| Aministration site condition - energy uncreased |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Aministration site condition - Fatifue |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Administration site condition - feeling hot |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Administration site condition - bruising |
1
16.7%
|
1
16.7%
|
1
16.7%
|
2
33.3%
|
3
33.3%
|
| Administration site condition - discolourization |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Administration site condition - Erythema |
6
100%
|
6
100%
|
4
66.7%
|
5
83.3%
|
8
88.9%
|
| Administration site condition - hemorrhage |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Administration site condition - injection mass |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Administration site condition - nodule |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Administration site condition- Edema |
6
100%
|
4
66.7%
|
6
100%
|
4
66.7%
|
5
55.6%
|
| Administration site condition - pain |
6
100%
|
5
83.3%
|
5
83.3%
|
5
83.3%
|
3
33.3%
|
| Administration site condition- pruritus |
2
33.3%
|
0
0%
|
0
0%
|
2
33.3%
|
0
0%
|
| Administration site condition - rash |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Administration site condition - warmth |
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Administration site condition medical device reac |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| general condition non cardiac chest pain |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Injury and procedure complications - skin abrasion |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Investigations - Electrodiagram QT prolonged |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Muscoloskeletal and connective tissue - myalgia |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Muscoloskeletal and connective tissue - pain extre |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
| Nervou system disorders- Dizziness |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Nervou system disorders - Headache |
2
33.3%
|
1
16.7%
|
2
33.3%
|
0
0%
|
1
11.1%
|
| Respeiratory, thoracic - oropharyngea pain |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Respeiratory, thoracic - Respiratory tracongestion |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Respeiratory, thoracic - Rhinorrhoea |
1
16.7%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| skin and subcutaneous tissue disorders - erythema |
0
0%
|
0
0%
|
3
50%
|
0
0%
|
0
0%
|
| skin and subcutaneous tissue disorders hyperhidros |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| skin and subcutaneous tissue disorders - pruritus |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Title | Efficacy: A Significant Thermogenesis at the Injected Site. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Day 28 |
5
83.3%
|
5
83.3%
|
3
50%
|
6
100%
|
1
11.1%
|
| Day 56 |
1
16.7%
|
3
50%
|
3
50%
|
6
100%
|
0
0%
|
| Day 84 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
4
66.7%
|
0
0%
|
| Day 112 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
5
83.3%
|
0
0%
|
| Day 140 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
4
66.7%
|
0
0%
|
| Day 168 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
3
50%
|
0
0%
|
| Title | Duration of the Thermogenic Effect From Day 28. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Mean (Standard Deviation) [days] |
5.6
(12.5)
|
16.8
(15.3)
|
5.6
(12.5)
|
107.3
(44.9)
|
0
(0)
|
| Title | Local Reduction in Fat Mass as Measured by MRI. Local Reduction in Fat Will be Measured by Periodically MRI Scans of the Abdomen. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| In cohort 4, one subjects was not analyzed due to MRI image quality (bubble) |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 5 | 7 |
| Day 28 |
-0.62
(5.17)
|
-9.15
(10.55)
|
-9.1
(4.27)
|
-14.68
(8.16)
|
2.94
(10.08)
|
| Day 56 |
NA
(NA)
|
-8.56
(8.85)
|
-10.52
(8.42)
|
-18.10
(10.93)
|
3.61
(3.48)
|
| Day 84 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
-12.75
(9.83)
|
-6.57
(9.78)
|
| Day 112 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
-16.10
(13.81)
|
-8.2
(11.54)
|
| Day 140 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
-12.46
(11.26)
|
-2.9
(0.45)
|
| Day 168 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
-14.32
(10.94)
|
-2.54
(8.57)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 1, Placebo |
|---|---|---|
| Comments | The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Kruskal-Wallis | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 2, Placebo |
|---|---|---|
| Comments | The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups, at day 28 and Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Kruskal-Wallis | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 3, Placebo |
|---|---|---|
| Comments | The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Kruskal-Wallis | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 4, Placebo |
|---|---|---|
| Comments | The Kruskal-Wallis T-test was applied for analyzing the difference in between the study groups | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Kruskal-Wallis | |
| Comments | ||
| Title | Changes in Fasting Blood Glucose From Baseline. |
|---|---|
| Description | Changes from baseline in fasting blood glucose by visit, treatment, and cohort. |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Day -1 |
86.7
(4.2)
|
91.3
(5.16)
|
91.7
(7.47)
|
90.8
(7.17)
|
93.2
(3.93)
|
| Day 56 |
93
(3.22)
|
92.8
(11.8)
|
93.3
(7.58)
|
93.7
(5.3)
|
94.6
(6.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 1, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 2, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 3, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 4, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Changes in Blood Lipid Profile From Baseline. |
|---|---|
| Description | Changes from baseline in lipid profile by visit, treatment, and cohort. |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | A single-time injection, multiple subcutaneous injections of 80 mg 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. | A single-time injection, multiple subcutaneous injections of 120 mg 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. | A single-time injection, multiple subcutaneous injections of 180 mg 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. | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Cholesterol Day -1 |
188
(32.8)
|
199
(11)
|
196
(41.4)
|
170.8
(23)
|
186.7
(19.8)
|
| Cholesterol Day 56 |
184
(39.8)
|
205
(29.7)
|
201.7
(46.1)
|
176
(28.6)
|
182.4
(19.3)
|
| HDL Day -1 |
43.5
(7.23)
|
44.33
(11.1)
|
41.5
(6)
|
44
(6.87)
|
42.44
(5.6)
|
| HDL Day 56 |
40
(9.44)
|
50.8
(14.2)
|
41.5
(9.9)
|
45.3
(5.05)
|
41.14
(7)
|
| LDL Day -1 |
129
(33.5)
|
126.5
(13.3)
|
134
(33)
|
105.5
(15)
|
116
(10.3)
|
| LDL Day 56 |
120
(31.3)
|
132
(23.9)
|
134.7
(37)
|
128
(0)
|
103
(14.8)
|
| Triglycerides Day -1 |
107.3
(42.3)
|
131
(77)
|
112.5
(58.9)
|
121.7
(39.3)
|
155.8
(98)
|
| Triglycerides Day 56 |
118
(85.4)
|
136
(61.1)
|
193.5
(16.7)
|
128.33
(55.4)
|
234
(220)
|
| Title | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. |
|---|---|
| Description | Averaged Cmax values by cohort. |
| Time Frame | 1-2 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 |
|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
84.15
(16.27)
|
181.89
(49.86)
|
241
(72.09)
|
344
(73.7)
|
| Title | Changes in Body Weight |
|---|---|
| Description | Changes from baseline in body weight by visit, treatment, and cohort. |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | A single-time injection, multiple subcutaneous injections of 80 mg 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. | A single-time injection, multiple subcutaneous injections of 120 mg 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. | A single-time injection, multiple subcutaneous injections of 180 mg 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. | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Weight Day -1 |
103.3
(11.1)
|
95.4
(6.9)
|
101.3
(20.3)
|
96.1
(12.6)
|
99.1
(8.1)
|
| Weight Day 56 |
104.4
(12.5)
|
96.1
(7.8)
|
103.4
(22.4)
|
96
(12.3)
|
101.2
(9.7)
|
| Title | Changes in Waist to Hip Ratio [WHR] |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | A single-time injection, multiple subcutaneous injections of 80 mg 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. | A single-time injection, multiple subcutaneous injections of 120 mg 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. | A single-time injection, multiple subcutaneous injections of 180 mg 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. | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 | 7 |
| Waist to hip ratio Day -1 |
1
(0.1)
|
1
(0)
|
1
(0.1)
|
1
(0)
|
1
(0.1)
|
| Waist to hip ratio Day 56 |
1
(0)
|
1
(0)
|
1
(0)
|
1
(0)
|
1
(0.1)
|
| Title | Elucidation of the Histological Changes Account for the Thermogenic Effect. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | RZL-012 Cohort 3 | Placebo |
|---|---|---|
| Arm/Group Description | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 2 | 1 |
| Count of Participants [Participants] |
2
33.3%
|
1
16.7%
|
| Title | Change From Baseline in Inflammatory Markers and Cytokines. Testing of Inflammatory Markers and Cytokines Will be Conducted by Blood Sampling. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was designed in a way that inflammation marker will be measured only for active and placebo subjects from cohorts 2-4 |
| Arm/Group Title | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 at 8/16/24/36 sites (0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 5 |
| CRP Day -1 (mg/dL) |
0.2
(0.13)
|
0.6
(1.08)
|
0.5
(0)
|
0.2
(0.1)
|
| CRP Day 28 (mg/dL) |
0.27
(0.31)
|
0.2
(0.12)
|
0.43
(0.15)
|
0.2
(0.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RZL-012 Cohort 3, RZL-012 Cohort 4 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Pharmacokinetics: Establishing Pharmacokinetic Profile of RZL-012. |
|---|---|
| Description | Averaged Tmax values by cohort. |
| Time Frame | 0.5, 1,2,3,4,5,6,8,12,16,24,30 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 |
|---|---|---|---|---|
| Arm/Group Description | A single-time injection, multiple subcutaneous injections of 40 RZL-012 administered into 8 sites (0.1mL per site): RZL-012: Subject receive a single-time injection. Multiple injections of RZL-012 are administered at doses of 40-180mg (8-36 injection sites, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180mg doses (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. | 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 40-180 mg (8-36 injections, 0.1mL per site) into the abdominal subcutaneous fat. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Hour] |
1.83
(0.41)
|
1.83
(0.41)
|
1.83
(0.41)
|
2
(0)
|
Adverse Events
| Time Frame | All reported adverse events were coded to a standard set of terms using MedDRA coding dictionary. Cohort 4 subjects were followed up for Adverse Events up to 168 days following injection. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | None of the subjects was reported with SAEs. None of the subjects died during the study | |||||||||
| Arm/Group Title | RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | |||||
| Arm/Group Description | 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. | A single-time injection, multiple subcutaneous injections of 80 mg 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. | A single-time injection, multiple subcutaneous injections of 120 mg 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. | A single-time injection, multiple subcutaneous injections of 180 mg 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. | A single-time injection, multiple subcutaneous injections of Placebo administered into 8/16/24/36 sites (0.1mL per site): Subject receive a single-time injection. Multiple injections of Placebo are administered at 8/16/24/36 (0.1mL per site) into the abdominal subcutaneous fat. | |||||
All Cause Mortality |
||||||||||
| RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/9 (0%) | |||||
Serious Adverse Events |
||||||||||
| RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/9 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| RZL-012 Cohort 1 | RZL-012 Cohort 2 | RZL-012 Cohort 3 | RZL-012 Cohort 4 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 9/9 (100%) | |||||
| Cardiac disorders | ||||||||||
| Ventricular extrasystoles | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| Ear and labyrinth disorders | ||||||||||
| ear pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| ear swelling | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| Hypoacusis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| Otorrhoea | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| General disorders | ||||||||||
| Energy increased | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| fatigue | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Feeling hot | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Injection site bruising | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 3/9 (33.3%) | 3 |
| Injection site discolouration | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/9 (0%) | 0 |
| Injection site Erythema | 6/6 (100%) | 6 | 6/6 (100%) | 7 | 4/6 (66.7%) | 5 | 5/6 (83.3%) | 7 | 8/9 (88.9%) | 11 |
| Injection site hemmorhage | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Injection site mass | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/9 (0%) | 0 |
| Injection site nodule | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/9 (0%) | 0 |
| Injection site Edema | 6/6 (100%) | 7 | 4/6 (66.7%) | 4 | 6/6 (100%) | 7 | 4/6 (66.7%) | 5 | 5/9 (55.6%) | 6 |
| Injection site pain | 6/6 (100%) | 6 | 5/6 (83.3%) | 5 | 5/6 (83.3%) | 8 | 5/6 (83.3%) | 6 | 3/9 (33.3%) | 3 |
| Injection site pruritus | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 0/9 (0%) | 0 |
| Injection site rash | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Injection site warmth | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Medical device reaction | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Non cardiac chest pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Skin abrasion | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Investigations | ||||||||||
| Electrocardiac QT prolonged | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Myalgia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Pain in extremity | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/9 (11.1%) | 1 |
| Nervous system disorders | ||||||||||
| Dizziness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Headache | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/9 (11.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Orpharyngeal pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Respiratory tract congestion | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Rhinorrhoea | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Erythema | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Hyperhidrosis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/9 (0%) | 0 |
| Pruritus | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/9 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Racheli Gueta - Clinical Trials Manager |
|---|---|
| Organization | Raziel Therapeutics |
| Phone | 972-8-9126941 |
| racheli@raziel-therapy.com |
Responsible Party:
Raziel Therapeutics Ltd.
ClinicalTrials.gov Identifier:
NCT03171415
Other Study ID Numbers:
- RZL-012-P2aUS-001
First Posted:
May 31, 2017
Last Update Posted:
Aug 21, 2019
Last Verified:
Sep 1, 2018